16-3590784-C-T

Position:

chr16-3590784-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032444.4(SLX4):c.2854G>A(p.Ala952Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 1,613,960 control chromosomes in the GnomAD database, including 3,721 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A952M) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.077 ( 483 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3238 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0130

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:

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=0.0015773475).

BP6

Variant 16-3590784-C-T is Benign according to our data. Variant chr16-3590784-C-T is described in ClinVar as [Benign]. Clinvar id is 262044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.2854G>A	p.Ala952Thr	missense_variant	12/15	ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.2854G>A	p.Ala952Thr	missense_variant	12/15	5	NM_032444.4	ENSP00000294008	P1	Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.0769

AC:

11706

AN:

152136

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0786

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0362

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0859

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0653

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0652

AC:

16376

AN:

251170

Hom.:

622

AF XY:

0.0627

AC XY:

8520

AN XY:

135794

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.0737

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0355

Gnomad SAS exome

AF:

0.0522

Gnomad FIN exome

AF:

0.0881

Gnomad NFE exome

AF:

0.0652

Gnomad OTH exome

AF:

0.0532

GnomAD4 exome

AF:

0.0641

AC:

93676

AN:

1461706

Hom.:

3238

Cov.:

AF XY:

0.0632

AC XY:

45972

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0710

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0317

Gnomad4 SAS exome

AF:

0.0534

Gnomad4 FIN exome

AF:

0.0829

Gnomad4 NFE exome

AF:

0.0650

Gnomad4 OTH exome

AF:

0.0621

GnomAD4 genome

AF:

0.0770

AC:

11716

AN:

152254

Hom.:

483

Cov.:

AF XY:

0.0773

AC XY:

5758

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.0783

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0361

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0859

Gnomad4 NFE

AF:

0.0653

Gnomad4 OTH

AF:

0.0677

Alfa

AF:

0.0536

Hom.:

149

Bravo

AF:

0.0787

TwinsUK

AF:

0.0599

AC:

222

ALSPAC

AF:

0.0607

AC:

234

ESP6500AA

AF:

0.108

AC:

476

ESP6500EA

AF:

0.0653

AC:

562

ExAC

AF:

0.0671

AC:

8147

Asia WGS

AF:

0.0550

AC:

193

AN:

3478

EpiCase

AF:

0.0569

EpiControl

AF:

0.0584

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 19, 2016	- -

Fanconi anemia complementation group P

Benign:2

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

DANN

Benign

0.79

DEOGEN2

Benign

0.037

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.51

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.64

REVEL

Benign

0.021

Sift

Benign

0.23

Sift4G

Benign

0.22

Polyphen

0.056

Vest4

0.025

MPC

0.083

ClinPred

0.0013

GERP RS

-1.4

Varity_R

0.029

gMVP

0.12

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