NM_014600.3:c.*157T>C

Variant names:

• chr2-31266861-T-C
• rs644926
• NM_014600.3:c.*157T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014600.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	NM_014600.3	MANE Select	c.*157T>C		3_prime_UTR	Exon 6 of 6	NP_055415.1	Q9NZN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHD3	ENST00000322054.10	TSL:1 MANE Select	c.*157T>C		3_prime_UTR	Exon 6 of 6	ENSP00000327116.5	Q9NZN3-1
	EHD3	ENST00000907587.1		c.*157T>C		3_prime_UTR	Exon 8 of 8	ENSP00000577646.1
	EHD3	ENST00000907586.1		c.*157T>C		3_prime_UTR	Exon 8 of 8	ENSP00000577645.1

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

African (AFR) AF: 0.958 AC: 18328 AN: 19126

American (AMR) AF: 0.904 AC: 16553 AN: 18310

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 13364 AN: 15424

East Asian (EAS) AF: 0.953 AC: 30539 AN: 32060

South Asian (SAS) AF: 0.856 AC: 39611 AN: 46292

European-Finnish (FIN) AF: 0.812 AC: 23733 AN: 29242

Middle Eastern (MID) AF: 0.867 AC: 2361 AN: 2722

European-Non Finnish (NFE) AF: 0.790 AC: 474957 AN: 601122

Other (OTH) AF: 0.827 AC: 31086 AN: 37594

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

African (AFR) AF: 0.952 AC: 39469 AN: 41456

American (AMR) AF: 0.894 AC: 13657 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2971 AN: 3470

East Asian (EAS) AF: 0.949 AC: 4890 AN: 5154

South Asian (SAS) AF: 0.860 AC: 4106 AN: 4772

European-Finnish (FIN) AF: 0.821 AC: 8649 AN: 10538

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.791 AC: 53769 AN: 67962

Other (OTH) AF: 0.867 AC: 1823 AN: 2102

Alfa AF: 0.819 Hom.: 70557

Bravo AF: 0.869

Asia WGS AF: 0.915 AC: 3185 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.31
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs644926; hg19: chr2-31489727;