Variant 10-24999541-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145010.4(ENKUR):c.83T>A(p.Ile28Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00373 in 1,604,076 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0036 ( 40 hom. )

Consequence

ENKUR
NM_145010.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.233

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:

THNSL1 (HGNC:):

THNSL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004059851).

BP6

Variant 10-24999541-A-T is Benign according to our data. Variant chr10-24999541-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640358.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENKUR	NM_145010.4 linkuse as main transcript	c.83T>A	p.Ile28Lys	missense_variant	2/6	ENST00000331161.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENKUR	ENST00000331161.9 linkuse as main transcript	c.83T>A	p.Ile28Lys	missense_variant	2/6	1	NM_145010.4	P4

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

737

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0321

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00531

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00505

AC:

1231

AN:

243536

Hom.:

AF XY:

0.00491

AC XY:

645

AN XY:

131462

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.000738

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000213

Gnomad FIN exome

AF:

0.0294

Gnomad NFE exome

AF:

0.00489

Gnomad OTH exome

AF:

0.00249

GnomAD4 exome

AF:

0.00362

AC:

5249

AN:

1451732

Hom.:

Cov.:

AF XY:

0.00360

AC XY:

2595

AN XY:

721792

show subpopulations

Gnomad4 AFR exome

AF:

0.000488

Gnomad4 AMR exome

AF:

0.000640

Gnomad4 ASJ exome

AF:

0.0000772

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000180

Gnomad4 FIN exome

AF:

0.0274

Gnomad4 NFE exome

AF:

0.00322

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00484

AC:

737

AN:

152344

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.0321

Gnomad4 NFE

AF:

0.00531

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00198

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00463

AC:

562

Asia WGS

AF:

0.000867

AC:

AN:

3474

EpiCase

AF:

0.00344

EpiControl

AF:

0.00338

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

ENKUR: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

Cadd

Benign

0.66

Dann

Benign

0.58

DEOGEN2

Benign

0.0058

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.089

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.61

N;N

REVEL

Benign

0.031

Sift

Benign

1.0

T;T

Sift4G

Benign

0.33

T;T

Polyphen

0.0070

B;.

Vest4

0.20

MVP

0.12

MPC

0.049

ClinPred

0.0060

GERP RS

-9.3

Varity_R

0.046

gMVP

0.35

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over