Variant 16-67665046-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032140.3(ENKD1):c.403C>T(p.Arg135Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,613,098 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: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ENKD1
NM_032140.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Variant links:

Genes affected

ENKD1 (HGNC:25246): (enkurin domain containing 1) Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

ENKD1 links:

ENKD1 (HGNC:):

ENKD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24198085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENKD1	NM_032140.3 linkuse as main transcript	c.403C>T	p.Arg135Cys	missense_variant	3/7	ENST00000243878.9	NP_115516.1	Q9H0I2-1
ENKD1	XM_024450469.2 linkuse as main transcript	c.403C>T	p.Arg135Cys	missense_variant	3/6		XP_024306237.1
ENKD1	XM_024450470.2 linkuse as main transcript	c.403C>T	p.Arg135Cys	missense_variant	3/6		XP_024306238.1
ENKD1	NR_138150.2 linkuse as main transcript	n.589-984C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENKD1	ENST00000243878.9 linkuse as main transcript	c.403C>T	p.Arg135Cys	missense_variant	3/7	1	NM_032140.3	ENSP00000243878.4		Q9H0I2-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000519

AC:

AN:

250430

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000378

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1460902

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000337

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.403C>T (p.R135C) alteration is located in exon 3 (coding exon 3) of the ENKD1 gene. This alteration results from a C to T substitution at nucleotide position 403, causing the arginine (R) at amino acid position 135 to be replaced by a cysteine (C). 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

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.081

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.0052

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.091

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.99

D;.

Vest4

0.52

MutPred

0.26

Loss of MoRF binding (P = 0.0534);Loss of MoRF binding (P = 0.0534);

MVP

0.76

MPC

0.69

ClinPred

0.60

GERP RS

4.6

Varity_R

0.23

gMVP

0.26

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