Variant chr9-114337121-T-C 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.4253A>G(p.Gln1418Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,454,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

AKNA
NM_001317950.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.442

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:

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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=0.016495496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKNA	NM_001317950.2 linkuse as main transcript	c.4253A>G	p.Gln1418Arg	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.4253A>G	p.Gln1418Arg	missense_variant	22/22	2	NM_001317950.2	ENSP00000363201.3		Q7Z591-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000821

AC:

AN:

243480

Hom.:

AF XY:

0.0000302

AC XY:

AN XY:

132472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000540

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:

0.00000911

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1454672

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723452

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000475

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000906

AC:

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

Aug 02, 2022

The c.4253A>G (p.Q1418R) alteration is located in exon 22 (coding exon 21) of the AKNA gene. This alteration results from a A to G substitution at nucleotide position 4253, causing the glutamine (Q) at amino acid position 1418 to be replaced by an arginine (R). 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

0.077

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0035

T;T;.;.;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.53

T;.;T;T;T

M_CAP

Benign

0.0047

MetaRNN

Benign

0.016

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

L;L;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.6

N;N;N;N;N

REVEL

Benign

0.028

Sift

Benign

0.14

T;T;T;T;T

Sift4G

Benign

0.40

T;T;T;T;T

Polyphen

0.0020

B;B;.;.;B

Vest4

0.10

MutPred

0.10

Gain of methylation at R1420 (P = 0.0792);Gain of methylation at R1420 (P = 0.0792);.;.;.;

MVP

0.31

MPC

0.074

ClinPred

0.015

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.062

gMVP

0.17

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