16-13920254-A-G

Position:

• chr16-13920254-A-G

Variant summary

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

The NM_005236.3(ERCC4):​c.89A>G​(p.Asp30Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ERCC4 NM_005236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39

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]

ERCC4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.89A>G	p.Asp30Gly	missense_variant	1/11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.89A>G	p.Asp30Gly	missense_variant	1/12		XP_011520726.1
LOC105371093	XR_007064999.1	n.82+6271T>C		intron_variant
LOC105371093	XR_007065000.1	n.82+6271T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.89A>G	p.Asp30Gly	missense_variant	1/11	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455100 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 724216

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	.;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.6	.;D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0050	.;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.98	.;D
Vest4		0.57
MutPred		0.67		Loss of stability (P = 0.0201);Loss of stability (P = 0.0201);
MVP		0.83
MPC		0.51
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.83
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr16-14014111;