rs116781836

Positions:

chr16-3589675-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032444.4(SLX4):c.3963G>A(p.Pro1321Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00605 in 1,613,938 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 129 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.936

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 16-3589675-C-T is Benign according to our data. Variant chr16-3589675-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3589675-C-T is described in Lovd as [Benign]. Variant chr16-3589675-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.936 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00883 (1344/152242) while in subpopulation SAS AF= 0.0448 (216/4820). AF 95% confidence interval is 0.0399. There are 15 homozygotes in gnomad4. There are 687 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.3963G>A	p.Pro1321Pro	synonymous_variant	12/15	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.3963G>A	p.Pro1321Pro	synonymous_variant	12/15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.00882

AC:

1342

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0179

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00505

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0456

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00325

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00916

AC:

2301

AN:

251260

Hom.:

AF XY:

0.0107

AC XY:

1458

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0169

Gnomad AMR exome

AF:

0.00477

Gnomad ASJ exome

AF:

0.0135

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0412

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00357

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.00576

AC:

8416

AN:

1461696

Hom.:

129

Cov.:

AF XY:

0.00694

AC XY:

5044

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.0117

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0439

Gnomad4 FIN exome

AF:

0.000413

Gnomad4 NFE exome

AF:

0.00255

Gnomad4 OTH exome

AF:

0.00767

GnomAD4 genome

AF:

0.00883

AC:

1344

AN:

152242

Hom.:

Cov.:

AF XY:

0.00923

AC XY:

687

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0448

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00535

Hom.:

Bravo

AF:

0.00826

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.00600

EpiControl

AF:

0.00533

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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 specified

Benign:2

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	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 26, 2021	- -
Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.9

DANN

Benign

0.54

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