16-3596179-C-T

Position:

chr16-3596179-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032444.4(SLX4):c.1898G>A(p.Gly633Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,551,708 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00081 ( 14 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.247

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 links:

SLX4 (HGNC:):

SLX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030311644).

BP6

Variant 16-3596179-C-T is Benign according to our data. Variant chr16-3596179-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00903 (1375/152332) while in subpopulation AFR AF= 0.0316 (1315/41574). AF 95% confidence interval is 0.0302. There are 20 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.1898G>A	p.Gly633Asp	missense_variant	8/15	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.1898G>A	p.Gly633Asp	missense_variant	8/15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.3119G>A		non_coding_transcript_exon_variant	6/7	1

Frequencies

GnomAD3 genomes

AF:

0.00900

AC:

1370

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00186

AC:

280

AN:

150800

Hom.:

AF XY:

0.00123

AC XY:

101

AN XY:

81928

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.000820

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000868

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000852

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000810

AC:

1133

AN:

1399376

Hom.:

Cov.:

AF XY:

0.000728

AC XY:

503

AN XY:

690972

show subpopulations

Gnomad4 AFR exome

AF:

0.0285

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000377

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000425

Gnomad4 OTH exome

AF:

0.00210

GnomAD4 genome

AF:

0.00903

AC:

1375

AN:

152332

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

626

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.000386

Hom.:

Bravo

AF:

0.0106

ESP6500AA

AF:

0.0217

AC:

ESP6500EA

AF:

0.000124

AC:

ExAC

AF:

0.00166

AC:

186

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia

Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Apr 28, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

Fanconi anemia complementation group P

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 24, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 07, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.5

DANN

Benign

0.60

DEOGEN2

Benign

0.062

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.1

REVEL

Benign

0.013

Sift

Benign

0.27

Sift4G

Benign

0.40

Polyphen

0.0090

Vest4

0.24

MVP

0.067

MPC

0.086

ClinPred

0.0015

GERP RS

-4.1

Varity_R

0.064

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over