chr16-3595468-C-G

Variant names:

• chr16-3595468-C-G
• rs80186343
• NM_032444.4:c.2013+137G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032444.4(SLX4):​c.2013+137G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 930,750 control chromosomes in the GnomAD database, including 1,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (410 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1524 hom.)
• Consequence: SLX4 NM_032444.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.34
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group P

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-3595468-C-G is Benign according to our data. Variant chr16-3595468-C-G is described in ClinVar as Benign. ClinVar VariationId is 929586.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4	c.2013+137G>C		intron_variant	Intron 9 of 14	ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4	c.2013+137G>C		intron_variant	Intron 9 of 14	5	NM_032444.4	ENSP00000294008.3
SLX4	ENST00000466154.5	n.*143G>C		downstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10969 AN: 152128 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0669

GnomAD4 exome AF: 0.0594 AC: 46205 AN: 778504 Hom.: 1524 AF XY: 0.0584 AC XY: 23695 AN XY: 405790

African (AFR) AF: 0.0842 AC: 1685 AN: 20006

American (AMR) AF: 0.0665 AC: 2349 AN: 35316

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 378 AN: 20724

East Asian (EAS) AF: 0.0306 AC: 1030 AN: 33676

South Asian (SAS) AF: 0.0510 AC: 3424 AN: 67106

European-Finnish (FIN) AF: 0.0781 AC: 2760 AN: 35328

Middle Eastern (MID) AF: 0.0307 AC: 87 AN: 2838

European-Non Finnish (NFE) AF: 0.0615 AC: 32311 AN: 525754

Other (OTH) AF: 0.0578 AC: 2181 AN: 37756

GnomAD4 genome AF: 0.0721 AC: 10983 AN: 152246 Hom.: 410 Cov.: 32 AF XY: 0.0726 AC XY: 5403 AN XY: 74438

African (AFR) AF: 0.0892 AC: 3704 AN: 41544

American (AMR) AF: 0.0756 AC: 1157 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5174

South Asian (SAS) AF: 0.0542 AC: 262 AN: 4832

European-Finnish (FIN) AF: 0.0868 AC: 921 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4458 AN: 67996

Other (OTH) AF: 0.0662 AC: 140 AN: 2114

Alfa AF: 0.0747 Hom.: 43

Bravo AF: 0.0731

Asia WGS AF: 0.0570 AC: 201 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 31, 2012

Leiden Open Variation Database

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

not provided Benign:1

Feb 24, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.28
DANN	Benign	0.71
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs80186343; hg19: chr16-3645469;