rs74640850

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032444.4(SLX4):c.555C>T(p.Asp185Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0604 in 1,613,964 control chromosomes in the GnomAD database, including 3,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 248 hom., cov: 32)

Exomes 𝑓: 0.061 ( 3038 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.127

Publications

13 publications found

Variant links:

Genes affected

SLX4 (HGNC:23845): (SLX4 structure-specific endonuclease subunit) This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia. [provided by RefSeq, Sep 2016]

SLX4 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group P
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SLX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-3606679-G-A is Benign according to our data. Variant chr16-3606679-G-A is described in ClinVar as Benign. ClinVar VariationId is 262055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.127 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.555C>T	p.Asp185Asp	synonymous_variant	Exon 3 of 15	ENST00000294008.4	NP_115820.2	Q8IY92-1
SLX4	XM_024450471.2 link	c.555C>T	p.Asp185Asp	synonymous_variant	Exon 3 of 15		XP_024306239.1
SLX4	XM_011522715.4 link	c.555C>T	p.Asp185Asp	synonymous_variant	Exon 3 of 15		XP_011521017.1
SLX4	XR_007064923.1 link	n.1204C>T		non_coding_transcript_exon_variant	Exon 3 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLX4	ENST00000294008.4 link	c.555C>T	p.Asp185Asp	synonymous_variant	Exon 3 of 15	5	NM_032444.4	ENSP00000294008.3	Q8IY92-1
SLX4	ENST00000466154.5 link	n.850C>T		non_coding_transcript_exon_variant	Exon 2 of 7	1
SLX4	ENST00000486524.1 link	n.1183C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
SLX4	ENST00000697858.1 link	n.-105C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0501

AC:

7624

AN:

152176

Hom.:

248

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0492

GnomAD2 exomes

AF:

0.0583

AC:

14658

AN:

251310

AF XY:

0.0579

show subpopulations

Gnomad AFR exome

AF:

0.0118

Gnomad AMR exome

AF:

0.0692

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0352

Gnomad FIN exome

AF:

0.0882

Gnomad NFE exome

AF:

0.0654

Gnomad OTH exome

AF:

0.0503

GnomAD4 exome

AF:

0.0615

AC:

89870

AN:

1461670

Hom.:

3038

Cov.:

AF XY:

0.0610

AC XY:

44334

AN XY:

727122

show subpopulations

African (AFR)

AF:

0.00905

AC:

303

AN:

33476

American (AMR)

AF:

0.0654

AC:

2923

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

494

AN:

26136

East Asian (EAS)

AF:

0.0318

AC:

1263

AN:

39700

South Asian (SAS)

AF:

0.0532

AC:

4585

AN:

86258

European-Finnish (FIN)

AF:

0.0831

AC:

4438

AN:

53382

Middle Eastern (MID)

AF:

0.0272

AC:

157

AN:

5764

European-Non Finnish (NFE)

AF:

0.0651

AC:

72338

AN:

1111844

Other (OTH)

AF:

0.0558

AC:

3369

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

4963

9925

14888

19850

24813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2618

5236

7854

10472

13090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0500

AC:

7620

AN:

152294

Hom.:

248

Cov.:

AF XY:

0.0515

AC XY:

3833

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0120

AC:

497

AN:

41562

American (AMR)

AF:

0.0684

AC:

1046

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.0365

AC:

189

AN:

5174

South Asian (SAS)

AF:

0.0536

AC:

259

AN:

4828

European-Finnish (FIN)

AF:

0.0867

AC:

920

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0655

AC:

4454

AN:

68040

Other (OTH)

AF:

0.0487

AC:

103

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

387

774

1161

1548

1935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0558

Hom.:

133

Bravo

AF:

0.0466

Asia WGS

AF:

0.0510

AC:

180

AN:

3478

EpiCase

AF:

0.0567

EpiControl

AF:

0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:3

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 12, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 31, 2012

Leiden Open Variation Database

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.7

(source)

DANN

Benign

0.68

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over