chr16-3597691-A-C

Position:

chr16-3597691-A-C

Variant summary

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

The NM_032444.4(SLX4):c.1371T>G(p.Asn457Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,612,600 control chromosomes in the GnomAD database, including 3,436 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 0.063 ( 319 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3117 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.525

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=0.0011074543).

BP6

Variant 16-3597691-A-C is Benign according to our data. Variant chr16-3597691-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 262035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3597691-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0699 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.1371T>G	p.Asn457Lys	missense_variant	7/15	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.1371T>G	p.Asn457Lys	missense_variant	7/15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.2592T>G		non_coding_transcript_exon_variant	5/7	1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9616

AN:

151934

Hom.:

318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0578

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0365

Gnomad SAS

AF:

0.0538

Gnomad FIN

AF:

0.0868

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0656

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0617

AC:

15404

AN:

249510

Hom.:

560

AF XY:

0.0605

AC XY:

8189

AN XY:

135426

show subpopulations

Gnomad AFR exome

AF:

0.0571

Gnomad AMR exome

AF:

0.0716

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0350

Gnomad SAS exome

AF:

0.0522

Gnomad FIN exome

AF:

0.0882

Gnomad NFE exome

AF:

0.0656

Gnomad OTH exome

AF:

0.0515

GnomAD4 exome

AF:

0.0630

AC:

92078

AN:

1460548

Hom.:

3117

Cov.:

AF XY:

0.0623

AC XY:

45293

AN XY:

726618

show subpopulations

Gnomad4 AFR exome

AF:

0.0580

Gnomad4 AMR exome

AF:

0.0685

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0316

Gnomad4 SAS exome

AF:

0.0535

Gnomad4 FIN exome

AF:

0.0834

Gnomad4 NFE exome

AF:

0.0653

Gnomad4 OTH exome

AF:

0.0594

GnomAD4 genome

AF:

0.0633

AC:

9625

AN:

152052

Hom.:

319

Cov.:

AF XY:

0.0644

AC XY:

4786

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0579

Gnomad4 AMR

AF:

0.0735

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0364

Gnomad4 SAS

AF:

0.0547

Gnomad4 FIN

AF:

0.0868

Gnomad4 NFE

AF:

0.0656

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0622

Hom.:

131

Bravo

AF:

0.0626

TwinsUK

AF:

0.0612

AC:

227

ALSPAC

AF:

0.0620

AC:

239

ESP6500AA

AF:

0.0602

AC:

264

ESP6500EA

AF:

0.0676

AC:

581

ExAC

AF:

0.0625

AC:

7583

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

EpiCase

AF:

0.0569

EpiControl

AF:

0.0586

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 28, 2016	- -
Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 31, 2012	Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

Fanconi anemia complementation group P

Benign:2

Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 22, 2019	- -

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.051

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0011

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.3

PrimateAI

Benign

0.43

PROVEAN

Benign

3.0

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.058

MutPred

0.15

Gain of methylation at N457 (P = 0.0151);

MPC

0.062

ClinPred

0.0042

GERP RS

5.2

Varity_R

0.078

gMVP

0.079

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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