Variant chr9-114337217-T-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_001317950.2(AKNA):c.4157A>T(p.His1386Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000699 in 1,587,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

AKNA
NM_001317950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40

Variant links:

Genes affected

AKNA (HGNC:24108): (AT-hook transcription factor) Predicted to enable DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in centrosome; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

AKNA 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=0.18927026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKNA	NM_001317950.2 linkuse as main transcript	c.4157A>T	p.His1386Leu	missense_variant	22/22	ENST00000374088.8	NP_001304879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKNA	ENST00000374088.8 linkuse as main transcript	c.4157A>T	p.His1386Leu	missense_variant	22/22	2	NM_001317950.2	ENSP00000363201	P3	Q7Z591-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000825

AC:

AN:

242340

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131286

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:

0.0000181

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000759

AC:

109

AN:

1435590

Hom.:

Cov.:

AF XY:

0.0000746

AC XY:

AN XY:

710124

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:

0.0000997

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000567

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000111

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 22, 2023

The c.4157A>T (p.H1386L) alteration is located in exon 22 (coding exon 21) of the AKNA gene. This alteration results from a A to T substitution at nucleotide position 4157, causing the histidine (H) at amino acid position 1386 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

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.45

CADD

Benign

6.8

DANN

Benign

0.95

DEOGEN2

Benign

0.049

T;T;.;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.64

T;.;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.;.;.

MutationTaster

Benign

0.93

N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-4.4

D;D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.010

D;D;D;D;D

Sift4G

Uncertain

0.044

D;D;D;D;D

Polyphen

0.90

P;P;.;.;P

Vest4

0.32

MutPred

0.31

Gain of methylation at R1382 (P = 0.1009);Gain of methylation at R1382 (P = 0.1009);.;.;.;

MVP

0.60

MPC

0.16

ClinPred

0.32

GERP RS

2.7

Varity_R

0.10

gMVP

0.27

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