Variant 9-114337091-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001317950.2(AKNA):c.4283G>A(p.Arg1428His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,489,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

AKNA
NM_001317950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

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:

AKNA (HGNC:):

AKNA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03698069).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKNA	NM_001317950.2 linkuse as main transcript	c.4283G>A	p.Arg1428His	missense_variant	22/22	ENST00000374088.8	NP_001304879.1	Q7Z591-1Q64FY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKNA	ENST00000374088.8 linkuse as main transcript	c.4283G>A	p.Arg1428His	missense_variant	22/22	2	NM_001317950.2	ENSP00000363201.3		Q7Z591-1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

145948

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:

0.000219

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000662

AC:

AN:

226542

Hom.:

AF XY:

0.0000722

AC XY:

AN XY:

124678

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000641

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000392

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1343320

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

666804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000401

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.0000238

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.000113

GnomAD4 genome

AF:

0.0000137

AC:

AN:

145948

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

70754

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000219

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000150

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000495

AC:

Asia WGS

AF:

0.00173

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

Feb 28, 2024

The c.4283G>A (p.R1428H) alteration is located in exon 22 (coding exon 21) of the AKNA gene. This alteration results from a G to A substitution at nucleotide position 4283, causing the arginine (R) at amino acid position 1428 to be replaced by a histidine (H). 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

0.092

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0070

T;T;.;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.87

D;.;D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.037

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.8

N;N;D;N;N

REVEL

Benign

0.028

Sift

Benign

0.15

T;T;T;T;T

Sift4G

Benign

0.33

T;T;D;D;T

Polyphen

0.072

B;B;.;.;B

Vest4

0.35

MutPred

0.25

Loss of MoRF binding (P = 0.0038);Loss of MoRF binding (P = 0.0038);.;.;.;

MVP

0.36

MPC

0.24

ClinPred

0.078

GERP RS

1.9

Varity_R

0.053

gMVP

0.068

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