Genetic Variant ENKUR:p.Arg229Gly (chr10-24984815-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_145010.4(ENKUR):c.685A>G(p.Arg229Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00555 in 1,613,864 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 27 hom. )

Consequence

ENKUR
NM_145010.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.32

Publications

6 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007371098).

BP6

Variant 10-24984815-T-C is Benign according to our data. Variant chr10-24984815-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2640357.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENKUR	NM_145010.4 link	c.685A>G	p.Arg229Gly	missense_variant	Exon 5 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.685A>G	p.Arg229Gly	missense_variant	Exon 5 of 6	1	NM_145010.4	ENSP00000331044.4		Q8TC29

Frequencies

GnomAD3 genomes

AF:

0.00503

AC:

766

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.0571

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00660

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00665

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00464

AC:

1165

AN:

251154

AF XY:

0.00459

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00342

Gnomad ASJ exome

AF:

0.00725

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00827

Gnomad NFE exome

AF:

0.00638

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00560

AC:

8187

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

4045

AN XY:

727084

show subpopulations

African (AFR)

AF:

0.000926

AC:

AN:

33470

American (AMR)

AF:

0.00378

AC:

169

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00765

AC:

200

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.000209

AC:

AN:

86208

European-Finnish (FIN)

AF:

0.00801

AC:

428

AN:

53400

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00633

AC:

7038

AN:

1111860

Other (OTH)

AF:

0.00492

AC:

297

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

397

794

1190

1587

1984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00502

AC:

765

AN:

152270

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41542

American (AMR)

AF:

0.00536

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00660

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00665

AC:

452

AN:

68012

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

127

170

212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00569

Hom.:

Bravo

AF:

0.00492

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00605

AC:

ExAC

AF:

0.00447

AC:

543

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00507

EpiControl

AF:

0.00498

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ENKUR: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

.;T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0074

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

1.3

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.3

D;.;D

REVEL

Benign

0.063

Sift

Uncertain

0.028

D;.;D

Sift4G

Uncertain

0.051

T;D;T

Polyphen

0.77

P;.;P

Vest4

0.27

MVP

0.17

MPC

0.093

ClinPred

0.055

GERP RS

5.3

Varity_R

0.28

gMVP

0.52

Mutation Taster

=94/6

polymorphism

(source)

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

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10-24984815-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over