Genetic Variant ENKUR:p.Asp38Glu (chr10-24999510-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145010.4(ENKUR):c.114C>G(p.Asp38Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,304 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ENKUR
NM_145010.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0110

Publications

0 publications found

Variant links:

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]

ENKUR links:

ENSG00000285859 (HGNC:):

ENSG00000285859 links:

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

THNSL1 links:

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ACMG classification

Classification was made for transcript

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=0.037970364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENKUR	NM_145010.4 link	c.114C>G	p.Asp38Glu	missense_variant	Exon 2 of 6	ENST00000331161.9	NP_659447.1	Q8TC29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENKUR	ENST00000331161.9 link	c.114C>G	p.Asp38Glu	missense_variant	Exon 2 of 6	1	NM_145010.4	ENSP00000331044.4		Q8TC29

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460304

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33402

American (AMR)

AF:

0.00

AC:

AN:

44526

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.00

AC:

AN:

85762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111442

Other (OTH)

AF:

0.00

AC:

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 13, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.114C>G (p.D38E) alteration is located in exon 2 (coding exon 2) of the ENKUR gene. This alteration results from a C to G substitution at nucleotide position 114, causing the aspartic acid (D) at amino acid position 38 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.6

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.0019

T;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.42

.;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.17

N;.

PhyloP100

-0.011

PrimateAI

Benign

0.38

PROVEAN

Benign

2.1

N;N

REVEL

Benign

0.23

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.053

MutPred

0.15

Gain of ubiquitination at K36 (P = 0.1123);Gain of ubiquitination at K36 (P = 0.1123);

MVP

0.095

MPC

0.033

ClinPred

0.069

GERP RS

0.50

Varity_R

0.059

gMVP

0.18

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over