2-31260876-C-T

Position:

• chr2-31260876-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014600.3(EHD3):​c.869C>T​(p.Ala290Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EHD3 NM_014600.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

Genes affected

EHD3 (HGNC:3244): (EH domain containing 3) Predicted to enable nucleic acid binding activity. Involved in several processes, including Golgi to lysosome transport; endosomal transport; and protein homooligomerization. Acts upstream of or within protein localization to plasma membrane and regulation of cardiac muscle cell membrane potential. Located in ciliary pocket membrane and recycling endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

LOC124905983 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD3	NM_014600.3	c.869C>T	p.Ala290Val	missense_variant	4/6	ENST00000322054.10	NP_055415.1
LOC124905983	XR_007086270.1	n.2573+2492G>A		intron_variant, non_coding_transcript_variant
EHD3	XM_011532806.3	c.230C>T	p.Ala77Val	missense_variant	2/4		XP_011531108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD3	ENST00000322054.10	c.869C>T	p.Ala290Val	missense_variant	4/6	1	NM_014600.3	ENSP00000327116	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.869C>T (p.A290V) alteration is located in exon 4 (coding exon 4) of the EHD3 gene. This alteration results from a C to T substitution at nucleotide position 869, causing the alanine (A) at amino acid position 290 to be replaced by a valine (V). 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	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.6	D
REVEL	Pathogenic	0.72
Sift	Benign	0.045	D
Sift4G	Benign	0.12	T
Polyphen		0.20	B
Vest4		0.76
MutPred		0.33		Gain of helix (P = 0.062);
MVP		0.96
MPC		0.43
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.53
gMVP		0.63

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: chr2-31483742;