rs2031938186

Variant names:

• chr16-13920182-C-G
• rs2031938186
• NM_005236.3:c.17C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-13920182-C-G
• chr16-13920182-C-T

Variant summary

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

The NM_005236.3(ERCC4):​c.17C>G​(p.Pro6Arg) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ERCC4 NM_005236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

Genes affected

ERCC4 (HGNC:3436): (ERCC excision repair 4, endonuclease catalytic subunit) The protein encoded by this gene forms a complex with ERCC1 and is involved in the 5' incision made during nucleotide excision repair. This complex is a structure specific DNA repair endonuclease that interacts with EME1. Defects in this gene are a cause of xeroderma pigmentosum complementation group F (XP-F), or xeroderma pigmentosum VI (XP6).[provided by RefSeq, Mar 2009]

LOC105371093 (HGNC:):

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=0.14128327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.17C>G	p.Pro6Arg	missense_variant	Exon 1 of 11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.17C>G	p.Pro6Arg	missense_variant	Exon 1 of 12		XP_011520726.1
LOC105371093	XR_007064999.1	n.82+6343G>C		intron_variant	Intron 1 of 2
LOC105371093	XR_007065000.1	n.82+6343G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.17C>G	p.Pro6Arg	missense_variant	Exon 1 of 11	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.78
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.66	.;N
REVEL	Benign	0.026
Sift	Uncertain	0.0080	.;D
Sift4G	Benign	0.066	T;T
Polyphen		0.0	.;B
Vest4		0.20
MutPred		0.40		Gain of MoRF binding (P = 0);Gain of MoRF binding (P = 0);
MVP		0.74
MPC		0.082
ClinPred		0.20	T
GERP RS		1.9
Varity_R		0.041
gMVP		0.45

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: rs2031938186; hg19: chr16-14014039;