11-64854665-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006795.4(EHD1):​c.1273G>A​(p.Gly425Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

EHD1
NM_006795.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83
Variant links:
Genes affected
EHD1 (HGNC:3242): (EH domain containing 1) This gene belongs to a highly conserved gene family encoding EPS15 homology (EH) domain-containing proteins. The protein-binding EH domain was first noted in EPS15, a substrate for the epidermal growth factor receptor. The EH domain has been shown to be an important motif in proteins involved in protein-protein interactions and in intracellular sorting. The protein encoded by this gene is thought to play a role in the endocytosis of IGF1 receptors. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.41970283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EHD1NM_006795.4 linkc.1273G>A p.Gly425Ser missense_variant Exon 5 of 5 ENST00000320631.8 NP_006786.2 Q9H4M9B2R5U3
EHD1NM_001282445.2 linkc.1315G>A p.Gly439Ser missense_variant Exon 6 of 6 NP_001269374.1 Q9H4M9A0A024R571
EHD1NM_001282444.2 linkc.1273G>A p.Gly425Ser missense_variant Exon 7 of 7 NP_001269373.1 Q9H4M9B2R5U3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EHD1ENST00000320631.8 linkc.1273G>A p.Gly425Ser missense_variant Exon 5 of 5 1 NM_006795.4 ENSP00000320516.3 Q9H4M9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250918
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135672
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461530
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727086
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1273G>A (p.G425S) alteration is located in exon 5 (coding exon 5) of the EHD1 gene. This alteration results from a G to A substitution at nucleotide position 1273, causing the glycine (G) at amino acid position 425 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Uncertain
0.020
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.30
T;T;T;.
Eigen
Benign
0.091
Eigen_PC
Benign
0.17
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
.;D;D;D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.42
T;T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Pathogenic
3.1
M;.;M;.
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.7
N;.;N;N
REVEL
Benign
0.19
Sift
Benign
0.28
T;.;T;T
Sift4G
Benign
0.34
T;T;T;T
Polyphen
0.037
B;.;B;.
Vest4
0.77
MutPred
0.32
Gain of relative solvent accessibility (P = 0.0249);.;Gain of relative solvent accessibility (P = 0.0249);.;
MVP
0.76
MPC
0.83
ClinPred
0.76
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.18
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs751688333; hg19: chr11-64622137; API