16-3590476-C-T

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.3162G>A(p.Ser1054Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 1,614,034 control chromosomes in the GnomAD database, including 1,255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1054S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.036 ( 185 hom., cov: 33)

Exomes 𝑓: 0.023 ( 1070 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.33

Publications

9 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=-0.73).

BP6

Variant 16-3590476-C-T is Benign according to our data. Variant chr16-3590476-C-T is described in ClinVar as Benign. ClinVar VariationId is 262046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.3162G>A	p.Ser1054Ser	synonymous_variant	Exon 12 of 15	ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 link	c.3162G>A	p.Ser1054Ser	synonymous_variant	Exon 12 of 15	5	NM_032444.4	ENSP00000294008.3

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5532

AN:

152136

Hom.:

184

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0795

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0448

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0320

GnomAD2 exomes

AF:

0.0329

AC:

8257

AN:

251130

AF XY:

0.0365

show subpopulations

Gnomad AFR exome

AF:

0.0786

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0179

Gnomad EAS exome

AF:

0.0497

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0253

GnomAD4 exome

AF:

0.0225

AC:

32940

AN:

1461780

Hom.:

1070

Cov.:

AF XY:

0.0251

AC XY:

18262

AN XY:

727164

show subpopulations

African (AFR)

AF:

0.0890

AC:

2981

AN:

33478

American (AMR)

AF:

0.0151

AC:

676

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0169

AC:

442

AN:

26132

East Asian (EAS)

AF:

0.0474

AC:

1880

AN:

39700

South Asian (SAS)

AF:

0.116

AC:

9968

AN:

86258

European-Finnish (FIN)

AF:

0.0131

AC:

699

AN:

53384

Middle Eastern (MID)

AF:

0.0348

AC:

201

AN:

5768

European-Non Finnish (NFE)

AF:

0.0128

AC:

14224

AN:

1111948

Other (OTH)

AF:

0.0309

AC:

1869

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2379

4758

7136

9515

11894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.0364

AC:

5535

AN:

152254

Hom.:

185

Cov.:

AF XY:

0.0375

AC XY:

2788

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0795

AC:

3301

AN:

41536

American (AMR)

AF:

0.0235

AC:

360

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3472

East Asian (EAS)

AF:

0.0451

AC:

233

AN:

5164

South Asian (SAS)

AF:

0.119

AC:

575

AN:

4826

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10618

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

764

AN:

68028

Other (OTH)

AF:

0.0317

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

254

507

761

1014

1268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0288

Hom.:

104

Bravo

AF:

0.0381

EpiCase

AF:

0.0152

EpiControl

AF:

0.0148

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

Jan 12, 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. -

Oct 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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 28, 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 03, 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

-0.73

CADD

Benign

0.54

(source)

DANN

Benign

0.55

PhyloP100

-5.3

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