rs146427260

Variant summary

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

The NM_000122.2(ERCC3):​c.2336G>T​(p.Arg779Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R779H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ERCC3
NM_000122.2 missense

Scores

4
6
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.70
Variant links:
Genes affected
ERCC3 (HGNC:3435): (ERCC excision repair 3, TFIIH core complex helicase subunit) This gene encodes an ATP-dependent DNA helicase that functions in nucleotide excision repair. The encoded protein is a subunit of basal transcription factor 2 (TFIIH) and, therefore, also functions in class II transcription. Mutations in this gene are associated with Xeroderma pigmentosum B, Cockayne's syndrome, and trichothiodystrophy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

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ACMG classification

Classification made for transcript

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
ERCC3NM_000122.2 linkc.2336G>T p.Arg779Leu missense_variant Exon 15 of 15 ENST00000285398.7 NP_000113.1 P19447

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ERCC3ENST00000285398.7 linkc.2336G>T p.Arg779Leu missense_variant Exon 15 of 15 1 NM_000122.2 ENSP00000285398.2 P19447

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Pathogenic
0.31
D
BayesDel_noAF
Pathogenic
0.21
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.028
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.069
D
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.9
N;.
REVEL
Uncertain
0.38
Sift
Benign
0.040
D;.
Sift4G
Uncertain
0.023
D;.
Polyphen
0.010
B;.
Vest4
0.75
MutPred
0.32
Loss of helix (P = 0.0626);.;
MVP
0.76
MPC
0.39
ClinPred
0.94
D
GERP RS
5.7
Varity_R
0.22
gMVP
0.59

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: chr2-128015185; API