7-43311968-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015052.5(HECW1):​c.233G>T​(p.Arg78Leu) 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. R78P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

HECW1
NM_015052.5 missense

Scores

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.89

Publications

2 publications found
Variant links:
Genes affected
HECW1 (HGNC:22195): (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; negative regulation of sodium ion transmembrane transporter activity; and regulation of dendrite morphogenesis. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
HECW1NM_015052.5 linkc.233G>T p.Arg78Leu missense_variant Exon 4 of 30 ENST00000395891.7 NP_055867.3 Q76N89-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HECW1ENST00000395891.7 linkc.233G>T p.Arg78Leu missense_variant Exon 4 of 30 1 NM_015052.5 ENSP00000379228.1 Q76N89-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
T;.
Eigen
Pathogenic
0.94
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Benign
0.021
T
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.3
M;M
PhyloP100
9.9
PrimateAI
Uncertain
0.79
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;.
Vest4
0.86
MutPred
0.35
Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);
MVP
0.50
MPC
1.6
ClinPred
0.99
D
GERP RS
5.8
Varity_R
0.58
gMVP
0.76
Mutation Taster
=14/86
disease causing

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

Other links and lift over

dbSNP: rs1283464320; hg19: chr7-43351567; API