16-3597892-G-C

Position:

• chr16-3597892-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032444.4(SLX4):​c.1271C>G​(p.Ala424Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A424V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLX4 NM_032444.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4	c.1271C>G	p.Ala424Gly	missense_variant	6/15	ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4	c.1271C>G	p.Ala424Gly	missense_variant	6/15	5	NM_032444.4	ENSP00000294008	P1
SLX4	ENST00000466154.5	n.2492C>G		non_coding_transcript_exon_variant	4/7	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.094	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.96	D
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.23
Sift	Uncertain	0.0070	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.31		Loss of helix (P = 0.0093);
MVP		0.50
MPC		0.36
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.38
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3647893;