rs144326379

Positions:

• chr16-3608626-A-C
• chr16-3608626-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_032444.4(SLX4):​c.339T>G​(p.Ser113=) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S113S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLX4 NM_032444.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP7: Synonymous conserved (PhyloP=-0.514 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4	c.339T>G	p.Ser113=	synonymous_variant	2/15	ENST00000294008.4	NP_115820.2
SLX4	XM_024450471.2	c.339T>G	p.Ser113=	synonymous_variant	2/15		XP_024306239.1
SLX4	XM_011522715.4	c.339T>G	p.Ser113=	synonymous_variant	2/15		XP_011521017.1
SLX4	XR_007064923.1	n.988T>G		non_coding_transcript_exon_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4	c.339T>G	p.Ser113=	synonymous_variant	2/15	5	NM_032444.4	ENSP00000294008	P1
SLX4	ENST00000466154.5	n.634T>G		non_coding_transcript_exon_variant	1/7	1
SLX4	ENST00000486524.1	n.967T>G		non_coding_transcript_exon_variant	2/4	2
SLX4	ENST00000697859.1	n.961T>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.76
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

Other links and lift over

dbSNP: rs144326379; hg19: chr16-3658627;