Variant chr16-67663497-G-A 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.803C>T(p.Pro268Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,612,494 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ENKD1
NM_032140.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

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.803C>T	p.Pro268Leu	missense_variant	6/7	ENST00000243878.9	NP_115516.1	Q9H0I2-1
ENKD1	XM_024450469.2 linkuse as main transcript	c.677C>T	p.Pro226Leu	missense_variant	5/6		XP_024306237.1
ENKD1	XM_024450470.2 linkuse as main transcript	c.*63C>T		3_prime_UTR_variant	6/6		XP_024306238.1
ENKD1	NR_138150.2 linkuse as main transcript	n.938C>T		non_coding_transcript_exon_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENKD1	ENST00000243878.9 linkuse as main transcript	c.803C>T	p.Pro268Leu	missense_variant	6/7	1	NM_032140.3	ENSP00000243878.4		Q9H0I2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00000406

AC:

AN:

246300

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133930

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460258

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726448

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Sep 20, 2023

The c.803C>T (p.P268L) alteration is located in exon 6 (coding exon 6) of the ENKD1 gene. This alteration results from a C to T substitution at nucleotide position 803, causing the proline (P) at amino acid position 268 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

Benign

0.11

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.76

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-6.9

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.35

MutPred

0.21

Loss of glycosylation at P268 (P = 0.0551);

MVP

0.77

MPC

0.24

ClinPred

0.99

GERP RS

3.8

Varity_R

0.63

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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