Genetic Variant NM_145010.4:c.568G>A (chr10-24990489-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_145010.4(ENKUR):c.568G>A(p.Asp190Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000609 in 1,460,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

ENKUR
NM_145010.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12

Publications

4 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: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32088614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENKUR	NM_145010.4 link	c.568G>A	p.Asp190Asn	missense_variant	Exon 4 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.568G>A	p.Asp190Asn	missense_variant	Exon 4 of 6	1	NM_145010.4	ENSP00000331044.4		Q8TC29

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000479

AC:

AN:

250548

AF XY:

0.0000443

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000609

AC:

AN:

1460920

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726736

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33414

American (AMR)

AF:

0.000202

AC:

AN:

44496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.0000465

AC:

AN:

85942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1111764

Other (OTH)

AF:

0.0000829

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 07, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.568G>A (p.D190N) alteration is located in exon 4 (coding exon 4) of the ENKUR gene. This alteration results from a G to A substitution at nucleotide position 568, causing the aspartic acid (D) at amino acid position 190 to be replaced by an asparagine (N). 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

0.081

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;.;T;T

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.75

.;T;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Uncertain

-0.19

MutationAssessor

Uncertain

2.5

M;.;.;.

PhyloP100

5.1

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.2

N;.;N;.

REVEL

Benign

0.16

Sift

Uncertain

0.027

D;.;D;.

Sift4G

Uncertain

0.021

D;D;D;.

Polyphen

1.0

D;.;D;.

Vest4

0.37

MVP

0.20

MPC

0.16

ClinPred

0.37

GERP RS

5.9

Varity_R

0.13

gMVP

0.37

Mutation Taster

=81/19

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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NM_145010.4:c.568G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over