rs76661336

chr16-3582229-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032444.4(SLX4):c.*113C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 840,902 control chromosomes in the GnomAD database, including 1,658 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (241 hom., cov: 32)
  • Exomes 𝑓: 0.060 (1417 hom.)
• Consequence: SLX4 NM_032444.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0920

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-3582229-G-A is Benign according to our data. Variant chr16-3582229-G-A is described in ClinVar as [Benign]. Clinvar id is 319141.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3582229-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLX4	NM_032444.4	c.*113C>T		3_prime_UTR_variant	15/15	ENST00000294008.4
SLX4	XM_011522715.4	c.*113C>T		3_prime_UTR_variant	15/15
SLX4	XM_024450471.2	c.*113C>T		3_prime_UTR_variant	15/15
SLX4	XM_047434801.1	c.*113C>T		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLX4	ENST00000294008.4	c.*113C>T		3_prime_UTR_variant	15/15	5	NM_032444.4	P1
	ENST00000573982.1	n.198+851G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7572 AN: 150098 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0690

Gnomad ASJ AF: 0.0188

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.0545

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.0488

GnomAD4 exome AF: 0.0600 AC: 41466 AN: 690698 Hom.: 1417 Cov.: 9 AF XY: 0.0595 AC XY: 21300 AN XY: 358018

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0648

Gnomad4 ASJ exome AF: 0.0187

Gnomad4 EAS exome AF: 0.0318

Gnomad4 SAS exome AF: 0.0532

Gnomad4 FIN exome AF: 0.0813

Gnomad4 NFE exome AF: 0.0654

Gnomad4 OTH exome AF: 0.0532

GnomAD4 genome AF: 0.0504 AC: 7568 AN: 150204 Hom.: 241 Cov.: 32 AF XY: 0.0519 AC XY: 3801 AN XY: 73298

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.0687

Gnomad4 ASJ AF: 0.0188

Gnomad4 EAS AF: 0.0371

Gnomad4 SAS AF: 0.0554

Gnomad4 FIN AF: 0.0910

Gnomad4 NFE AF: 0.0655

Gnomad4 OTH AF: 0.0479

Alfa AF: 0.0598 Hom.: 51

Bravo AF: 0.0465

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

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:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.9
Dann	Benign	0.73

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

Other links and lift over

dbSNP: rs76661336; hg19: chr16-3632230;