Variant 1-38991477-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000432648.8(AKIRIN1):c.97G>A(p.Gly33Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,424,910 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

AKIRIN1
ENST00000432648.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79

Variant links:

Genes affected

AKIRIN1 (HGNC:25744): (akirin 1) Predicted to enable transcription coregulator activity. Predicted to be involved in several processes, including myoblast migration involved in skeletal muscle regeneration; negative regulation of satellite cell differentiation; and positive regulation of lamellipodium assembly. Located in nuclear membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AKIRIN1 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=0.035879463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIRIN1	NM_024595.3 linkuse as main transcript	c.97G>A	p.Gly33Ser	missense_variant	1/5	ENST00000432648.8	NP_078871.1	Q9H9L7-1
AKIRIN1	NM_001136275.2 linkuse as main transcript	c.97G>A	p.Gly33Ser	missense_variant	1/4		NP_001129747.1	Q9H9L7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
AKIRIN1	ENST00000432648.8 linkuse as main transcript	c.97G>A	p.Gly33Ser	missense_variant	1/5	1	NM_024595.3	ENSP00000392678.3	Q9H9L7-1
AKIRIN1	ENST00000446189.6 linkuse as main transcript	c.97G>A	p.Gly33Ser	missense_variant	1/4	2		ENSP00000389866.2	Q9H9L7-2
AKIRIN1	ENST00000372984.8 linkuse as main transcript	c.97G>A	p.Gly33Ser	missense_variant	1/4	2		ENSP00000362075.4	B4DQP0
AKIRIN1	ENST00000531822.1 linkuse as main transcript	c.-21G>A		upstream_gene_variant		5		ENSP00000436372.1	H0YEQ5

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00140

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.0000670

AC:

AN:

44796

Hom.:

AF XY:

0.0000764

AC XY:

AN XY:

26176

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.000104

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:

0.0000660

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000519

AC:

AN:

1272680

Hom.:

Cov.:

AF XY:

0.0000417

AC XY:

AN XY:

624142

show subpopulations

Gnomad4 AFR exome

AF:

0.00199

Gnomad4 AMR exome

AF:

0.0000987

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000311

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000195

Gnomad4 OTH exome

AF:

0.000171

GnomAD4 genome

AF:

0.000434

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000487

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

Jul 26, 2022

The c.97G>A (p.G33S) alteration is located in exon 1 (coding exon 1) of the AKIRIN1 gene. This alteration results from a G to A substitution at nucleotide position 97, causing the glycine (G) at amino acid position 33 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

T;T;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.036

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

L;L;.

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.70

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.76

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.15

MutPred

0.23

Gain of glycosylation at G33 (P = 0.003);Gain of glycosylation at G33 (P = 0.003);Gain of glycosylation at G33 (P = 0.003);

MVP

0.082

MPC

1.1

ClinPred

0.062

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.25

gMVP

0.38

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