rs1555452514

Positions:

• chr16-3608933-C-A
• chr16-3608933-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032444.4(SLX4):​c.32G>T​(p.Gly11Val) variant causes a missense 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G11G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLX4 NM_032444.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.253

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14756846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLX4	NM_032444.4	c.32G>T	p.Gly11Val	missense_variant	2/15	ENST00000294008.4
SLX4	XM_024450471.2	c.32G>T	p.Gly11Val	missense_variant	2/15
SLX4	XM_011522715.4	c.32G>T	p.Gly11Val	missense_variant	2/15
SLX4	XR_007064923.1	n.681G>T		non_coding_transcript_exon_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLX4	ENST00000294008.4	c.32G>T	p.Gly11Val	missense_variant	2/15	5	NM_032444.4	P1
SLX4	ENST00000466154.5	n.327G>T		non_coding_transcript_exon_variant	1/7	1
SLX4	ENST00000486524.1	n.660G>T		non_coding_transcript_exon_variant	2/4	2
SLX4	ENST00000697859.1	n.654G>T		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.063
Sift	Benign	0.070	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.31
MutPred		0.46		Loss of disorder (P = 0.069);
MVP		0.26
MPC		0.091
ClinPred		0.33	T
GERP RS		0.22
Varity_R		0.050
gMVP		0.022

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: rs1555452514; hg19: chr16-3658934;