rs546878602

Variant names:

• chr10-24995854-C-T
• rs546878602
• NM_145010.4:c.239G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145010.4(ENKUR):​c.239G>A​(p.Arg80Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,603,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: ENKUR NM_145010.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

Genes affected

ENKUR (HGNC:28388): (enkurin, TRPC channel interacting protein) This gene encodes a protein that interacts with calmodulin and several transient receptor potential canonical cation channel proteins. The encoded protein may function as an adaptor to localize signal transduction machinery to calcium channels. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ENSG00000285859 (HGNC:):

THNSL1 (HGNC:26160): (threonine synthase like 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0551773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENKUR	NM_145010.4	c.239G>A	p.Arg80Gln	missense_variant	Exon 3 of 6	ENST00000331161.9	NP_659447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENKUR	ENST00000331161.9	c.239G>A	p.Arg80Gln	missense_variant	Exon 3 of 6	1	NM_145010.4	ENSP00000331044.4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152058 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000249 AC: 6 AN: 241398 AF XY: 0.0000153

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000450

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000317 AC: 46 AN: 1451254 Hom.: 0 Cov.: 30 AF XY: 0.0000305 AC XY: 22 AN XY: 721294

African (AFR) AF: 0.0000612 AC: 2 AN: 32700

American (AMR) AF: 0.0000236 AC: 1 AN: 42294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25660

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39610

South Asian (SAS) AF: 0.0000121 AC: 1 AN: 82892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.0000361 AC: 40 AN: 1109206

Other (OTH) AF: 0.00 AC: 0 AN: 59936

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152058 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74274

African (AFR) AF: 0.0000242 AC: 1 AN: 41386

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.000110

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.239G>A (p.R80Q) alteration is located in exon 3 (coding exon 3) of the ENKUR gene. This alteration results from a G to A substitution at nucleotide position 239, causing the arginine (R) at amino acid position 80 to be replaced by a glutamine (Q). 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	0.082
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	17
DANN	Benign	0.68
DEOGEN2	Benign	0.0013	T;.;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.69	.;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.055	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	N;.;.
PhyloP100		2.6
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.22	N;.;N
REVEL	Benign	0.091
Sift	Benign	0.59	T;.;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.017	B;.;B
Vest4		0.12
MutPred		0.26		Loss of MoRF binding (P = 0.0259);.;Loss of MoRF binding (P = 0.0259);
MVP		0.13
MPC		0.038
ClinPred		0.18	T
GERP RS		4.7
Varity_R		0.061
gMVP		0.16
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs546878602; hg19: chr10-25284783; COSMIC: COSV58633339;