Variant 20-10043151-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_022096.6(ANKEF1):c.376A>G(p.Lys126Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANKEF1
NM_022096.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

Variant links:

Genes affected

ANKEF1 (HGNC:15803): (ankyrin repeat and EF-hand domain containing 1) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ANKEF1 links:

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

SNAP25-AS1 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
ANKEF1	NM_022096.6 linkuse as main transcript	c.376A>G	p.Lys126Glu	missense_variant	4/11	ENST00000378392.6	NP_071379.3
SNAP25-AS1	NR_040710.1 linkuse as main transcript	n.500-16503T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKEF1	ENST00000378392.6 linkuse as main transcript	c.376A>G	p.Lys126Glu	missense_variant	4/11	1	NM_022096.6	ENSP00000367644	P1
SNAP25-AS1	ENST00000421143.6 linkuse as main transcript	n.235-16503T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251386

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135854

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727218

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

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

Feb 22, 2023

The c.376A>G (p.K126E) alteration is located in exon 4 (coding exon 2) of the ANKEF1 gene. This alteration results from a A to G substitution at nucleotide position 376, causing the lysine (K) at amino acid position 126 to be replaced by a glutamic acid (E). 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

0.16

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.011

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.77

.;T

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.50

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.16

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.98

D;D

Vest4

0.59

MutPred

0.53

Loss of catalytic residue at K126 (P = 0.0243);Loss of catalytic residue at K126 (P = 0.0243);

MVP

0.75

MPC

0.41

ClinPred

0.61

GERP RS

5.6

Varity_R

0.18

gMVP

0.63

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