rs1158728649

Positions:

• chr16-3582585-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_032444.4(SLX4):​c.5262G>A​(p.Glu1754=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLX4 NM_032444.4 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.456

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 16-3582585-C-T is Benign according to our data. Variant chr16-3582585-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 436776.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BP7: Synonymous conserved (PhyloP=0.456 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLX4	NM_032444.4	c.5262G>A	p.Glu1754=	synonymous_variant	15/15	ENST00000294008.4
SLX4	XM_024450471.2	c.5262G>A	p.Glu1754=	synonymous_variant	15/15
SLX4	XM_011522715.4	c.5259G>A	p.Glu1753=	synonymous_variant	15/15
SLX4	XM_047434801.1	c.4260G>A	p.Glu1420=	synonymous_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLX4	ENST00000294008.4	c.5262G>A	p.Glu1754=	synonymous_variant	15/15	5	NM_032444.4	P1
	ENST00000573982.1	n.199-551C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 12, 2016

- -

Fanconi anemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	1.0
DANN	Benign	0.65

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: rs1158728649; hg19: chr16-3632586;