16-13922083-G-T

Variant names:

• chr16-13922083-G-T
• NM_005236.3:c.260G>T

Variant summary

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

The NM_005236.3(ERCC4):​c.260G>T​(p.Arg87Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ERCC4 NM_005236.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

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:):

RPS26P52 (HGNC:36863): (ribosomal protein S26 pseudogene 52)

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 rank	MANE	Protein	UniProt
ERCC4	NM_005236.3	c.260G>T	p.Arg87Leu	missense_variant	Exon 2 of 11	ENST00000311895.8	NP_005227.1
ERCC4	XM_011522424.4	c.260G>T	p.Arg87Leu	missense_variant	Exon 2 of 12		XP_011520726.1
LOC105371093	XR_007064999.1	n.82+4442C>A		intron_variant	Intron 1 of 2
LOC105371093	XR_007065000.1	n.82+4442C>A		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC4	ENST00000311895.8	c.260G>T	p.Arg87Leu	missense_variant	Exon 2 of 11	1	NM_005236.3	ENSP00000310520.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461496 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727068

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.029
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.61	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.90	.;N
REVEL	Benign	0.099
Sift	Benign	0.42	.;T
Sift4G	Benign	0.54	T;T
Polyphen		0.031	.;B
Vest4		0.69
MutPred		0.52		Loss of disorder (P = 0.0365);Loss of disorder (P = 0.0365);
MVP		0.76
MPC		0.11
ClinPred		0.67	D
GERP RS		4.4
Varity_R		0.16
gMVP		0.70

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-14015940;