16-3600986-T-C

Position:

chr16-3600986-T-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.1156A>G(p.Met386Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,030 control chromosomes in the GnomAD database, including 3,410 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 (★★).

Frequency

Genomes: 𝑓 0.063 ( 320 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3090 hom. )

Consequence

SLX4
NM_032444.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.353

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=0.0031724274).

BP6

Variant 16-3600986-T-C is Benign according to our data. Variant chr16-3600986-T-C is described in ClinVar as [Benign]. Clinvar id is 262032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3600986-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0701 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.1156A>G	p.Met386Val	missense_variant	5/15	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.1156A>G	p.Met386Val	missense_variant	5/15	5	NM_032444.4	ENSP00000294008.3	Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.2377A>G		non_coding_transcript_exon_variant	3/7	1
SLX4	ENST00000486524.1 linkuse as main transcript	n.2710A>G		non_coding_transcript_exon_variant	4/4	2
SLX4	ENST00000697858.1 linkuse as main transcript	n.497A>G		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.0632

AC:

9607

AN:

152030

Hom.:

319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0739

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0863

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0580

GnomAD3 exomes

AF:

0.0612

AC:

15305

AN:

250000

Hom.:

523

AF XY:

0.0601

AC XY:

8129

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.0570

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0349

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0871

Gnomad NFE exome

AF:

0.0649

Gnomad OTH exome

AF:

0.0517

GnomAD4 exome

AF:

0.0628

AC:

91682

AN:

1460882

Hom.:

3090

Cov.:

AF XY:

0.0621

AC XY:

45108

AN XY:

726780

show subpopulations

Gnomad4 AFR exome

AF:

0.0579

Gnomad4 AMR exome

AF:

0.0682

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0319

Gnomad4 SAS exome

AF:

0.0533

Gnomad4 FIN exome

AF:

0.0829

Gnomad4 NFE exome

AF:

0.0650

Gnomad4 OTH exome

AF:

0.0589

GnomAD4 genome

AF:

0.0632

AC:

9616

AN:

152148

Hom.:

320

Cov.:

AF XY:

0.0643

AC XY:

4784

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0578

Gnomad4 AMR

AF:

0.0736

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0365

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0863

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.0574

Alfa

AF:

0.0597

Hom.:

405

Bravo

AF:

0.0626

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0618

AC:

238

ESP6500AA

AF:

0.0617

AC:

271

ESP6500EA

AF:

0.0669

AC:

575

ExAC

AF:

0.0623

AC:

7562

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

EpiCase

AF:

0.0568

EpiControl

AF:

0.0583

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 31, 2012	Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

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

Fanconi anemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Fanconi anemia complementation group P

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.51

DANN

Benign

0.36

DEOGEN2

Benign

0.014

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.35

PROVEAN

Benign

0.65

REVEL

Benign

0.051

Sift

Benign

0.65

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.022

MPC

0.056

ClinPred

0.00079

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.042

gMVP

0.18

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