chr16-3600990-T-C

Position:

chr16-3600990-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032444.4(SLX4):c.1152A>G(p.Pro384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,138 control chromosomes in the GnomAD database, including 3,407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 318 hom., cov: 31)

Exomes 𝑓: 0.063 ( 3089 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.51

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 16-3600990-T-C is Benign according to our data. Variant chr16-3600990-T-C is described in ClinVar as [Benign]. Clinvar id is 262030.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3600990-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-3.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.1152A>G	p.Pro384=	synonymous_variant	5/15	ENST00000294008.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.1152A>G	p.Pro384=	synonymous_variant	5/15	5	NM_032444.4	P1	Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript	n.2373A>G		non_coding_transcript_exon_variant	3/7	1
SLX4	ENST00000486524.1 linkuse as main transcript	n.2706A>G		non_coding_transcript_exon_variant	4/4	2
SLX4	ENST00000697858.1 linkuse as main transcript	n.493A>G		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.0632

AC:

9606

AN:

152032

Hom.:

316

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0577

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0366

Gnomad SAS

AF:

0.0531

Gnomad FIN

AF:

0.0863

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0584

GnomAD3 exomes

AF:

0.0613

AC:

15331

AN:

250078

Hom.:

528

AF XY:

0.0601

AC XY:

8132

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.0573

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0350

Gnomad SAS exome

AF:

0.0520

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0650

Gnomad OTH exome

AF:

0.0517

GnomAD4 exome

AF:

0.0628

AC:

91737

AN:

1460988

Hom.:

3089

Cov.:

AF XY:

0.0621

AC XY:

45129

AN XY:

726822

show subpopulations

Gnomad4 AFR exome

AF:

0.0580

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:

0.0590

GnomAD4 genome

AF:

0.0632

AC:

9616

AN:

152150

Hom.:

318

Cov.:

AF XY:

0.0643

AC XY:

4784

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0578

Gnomad4 AMR

AF:

0.0735

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0365

Gnomad4 SAS

AF:

0.0539

Gnomad4 FIN

AF:

0.0863

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0615

Hom.:

145

Bravo

AF:

0.0626

Asia WGS

AF:

0.0570

AC:

198

AN:

3478

EpiCase

AF:

0.0568

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: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. -

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

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

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.079

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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