rs112511042

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.1152A>G(p.Pro384Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,138 control chromosomes in the GnomAD database, including 3,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 318 hom., cov: 31)

Exomes 𝑓: 0.063 ( 3089 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.51

Publications

12 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=-0.97).

BP6

Variant 16-3600990-T-C is Benign according to our data. Variant chr16-3600990-T-C is described in ClinVar as Benign. ClinVar VariationId is 262030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.1152A>G	p.Pro384Pro	synonymous_variant	Exon 5 of 15	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLX4	ENST00000294008.4 link	c.1152A>G	p.Pro384Pro	synonymous_variant	Exon 5 of 15	5	NM_032444.4	ENSP00000294008.3	Q8IY92-1
SLX4	ENST00000466154.5 link	n.2373A>G		non_coding_transcript_exon_variant	Exon 3 of 7	1
SLX4	ENST00000486524.1 link	n.2706A>G		non_coding_transcript_exon_variant	Exon 4 of 4	2
SLX4	ENST00000697858.1 link	n.493A>G		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0632

AC:

9606

AN:

152032

Hom.:

316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0531

Gnomad FIN

AF:

0.0863

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0584

GnomAD2 exomes

AF:

0.0613

AC:

15331

AN:

250078

AF XY:

0.0601

show subpopulations

Gnomad AFR exome

AF:

0.0573

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0350

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0650

Gnomad OTH exome

AF:

0.0517

GnomAD4 exome

AF:

0.0628

AC:

91737

AN:

1460988

Hom.:

3089

Cov.:

AF XY:

0.0621

AC XY:

45129

AN XY:

726822

show subpopulations

African (AFR)

AF:

0.0580

AC:

1940

AN:

33466

American (AMR)

AF:

0.0682

AC:

3049

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

494

AN:

26136

East Asian (EAS)

AF:

0.0319

AC:

1266

AN:

39700

South Asian (SAS)

AF:

0.0533

AC:

4594

AN:

86228

European-Finnish (FIN)

AF:

0.0829

AC:

4408

AN:

53166

Middle Eastern (MID)

AF:

0.0291

AC:

163

AN:

5598

European-Non Finnish (NFE)

AF:

0.0650

AC:

72263

AN:

1111624

Other (OTH)

AF:

0.0590

AC:

3560

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

4980

9959

14939

19918

24898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2642

5284

7926

10568

13210

<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:

0.0632

AC:

9616

AN:

152150

Hom.:

318

Cov.:

AF XY:

0.0643

AC XY:

4784

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0578

AC:

2400

AN:

41498

American (AMR)

AF:

0.0735

AC:

1124

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3468

East Asian (EAS)

AF:

0.0365

AC:

189

AN:

5174

South Asian (SAS)

AF:

0.0539

AC:

260

AN:

4820

European-Finnish (FIN)

AF:

0.0863

AC:

913

AN:

10582

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0655

AC:

4456

AN:

68002

Other (OTH)

AF:

0.0578

AC:

122

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

479

959

1438

1918

2397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0614

Hom.:

147

Bravo

AF:

0.0626

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

EpiCase

AF:

0.0568

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

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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. -

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

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

-0.97

CADD

Benign

0.079

(source)

DANN

Benign

0.34

PhyloP100

-3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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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