10-24995863-T-C

Variant names:

• chr10-24995863-T-C
• NM_145010.4:c.230A>G

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.230A>G​(p.Asn77Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: ENKUR NM_145010.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.597
• 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=0.04124984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENKUR	NM_145010.4	c.230A>G	p.Asn77Ser	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.230A>G	p.Asn77Ser	missense_variant	Exon 3 of 6	1	NM_145010.4	ENSP00000331044.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230A>G (p.N77S) alteration is located in exon 3 (coding exon 3) of the ENKUR gene. This alteration results from a A to G substitution at nucleotide position 230, causing the asparagine (N) at amino acid position 77 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	0.070
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.4
DANN	Benign	0.43
DEOGEN2	Benign	0.00094	T;.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.58
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.34	.;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.041	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N;.;.
PhyloP100		0.60
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.13	N;.;N
REVEL	Benign	0.033
Sift	Benign	0.27	T;.;T
Sift4G	Benign	0.46	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.069
MutPred		0.13		Gain of phosphorylation at N77 (P = 0.0077);.;Gain of phosphorylation at N77 (P = 0.0077);
MVP		0.067
MPC		0.030
ClinPred		0.095	T
GERP RS		1.9
Varity_R		0.033
gMVP		0.12
Mutation Taster		=96/4	polymorphism

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

hg19: chr10-25284792;