rs644926

Positions:

• chr2-31266861-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014600.3(EHD3):​c.*157T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 953,836 control chromosomes in the GnomAD database, including 321,511 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56315 hom., cov: 29)
  • Exomes 𝑓: 0.81 (265196 hom.)
• Consequence: EHD3 NM_014600.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EHD3	NM_014600.3	c.*157T>C		3_prime_UTR_variant	6/6	ENST00000322054.10	NP_055415.1
EHD3	XM_011532806.3	c.*157T>C		3_prime_UTR_variant	4/4		XP_011531108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EHD3	ENST00000322054.10	c.*157T>C		3_prime_UTR_variant	6/6	1	NM_014600.3	ENSP00000327116	P1

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130217 AN: 151826 Hom.: 56252 Cov.: 29

Gnomad AFR AF: 0.952

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.866

GnomAD4 exome AF: 0.811 AC: 650532 AN: 801892 Hom.: 265196 Cov.: 10 AF XY: 0.812 AC XY: 324457 AN XY: 399612

Gnomad4 AFR exome AF: 0.958

Gnomad4 AMR exome AF: 0.904

Gnomad4 ASJ exome AF: 0.866

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.856

Gnomad4 FIN exome AF: 0.812

Gnomad4 NFE exome AF: 0.790

Gnomad4 OTH exome AF: 0.827

GnomAD4 genome AF: 0.858 AC: 130339 AN: 151944 Hom.: 56315 Cov.: 29 AF XY: 0.861 AC XY: 63935 AN XY: 74216

Gnomad4 AFR AF: 0.952

Gnomad4 AMR AF: 0.894

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.867

Alfa AF: 0.814 Hom.: 49853

Bravo AF: 0.869

Asia WGS AF: 0.915 AC: 3185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs644926; hg19: chr2-31489727;