Variant 16-67664026-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032140.3(ENKD1):c.490T>C(p.Phe164Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000425 in 1,412,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ENKD1
NM_032140.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ENKD1	NM_032140.3 linkuse as main transcript	c.490T>C	p.Phe164Leu	missense_variant	4/7	ENST00000243878.9	NP_115516.1	Q9H0I2-1
ENKD1	XM_024450470.2 linkuse as main transcript	c.490T>C	p.Phe164Leu	missense_variant	4/6		XP_024306238.1
ENKD1	XM_024450469.2 linkuse as main transcript	c.454-206T>C		intron_variant			XP_024306237.1
ENKD1	NR_138150.2 linkuse as main transcript	n.625T>C		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENKD1	ENST00000243878.9 linkuse as main transcript	c.490T>C	p.Phe164Leu	missense_variant	4/7	1	NM_032140.3	ENSP00000243878.4		Q9H0I2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000116

AC:

AN:

172174

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91580

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000837

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000425

AC:

AN:

1412630

Hom.:

Cov.:

AF XY:

0.00000716

AC XY:

AN XY:

698130

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000373

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000513

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000254

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Mar 29, 2023

The c.490T>C (p.F164L) alteration is located in exon 4 (coding exon 4) of the ENKD1 gene. This alteration results from a T to C substitution at nucleotide position 490, causing the phenylalanine (F) at amino acid position 164 to be replaced by a leucine (L). 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.44

T;T

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.1

D;.

REVEL

Benign

0.12

Sift

Uncertain

0.018

D;.

Sift4G

Benign

0.20

T;D

Polyphen

0.98

D;.

Vest4

0.53

MutPred

0.33

Loss of catalytic residue at F164 (P = 0.0057);Loss of catalytic residue at F164 (P = 0.0057);

MVP

0.77

MPC

0.77

ClinPred

0.90

GERP RS

4.5

Varity_R

0.27

gMVP

0.39

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