Variant 1-38991496-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000432648.8(AKIRIN1):c.116G>C(p.Arg39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000759 in 1,449,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

AKIRIN1
ENST00000432648.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81

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 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=0.11159101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIRIN1	NM_024595.3 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant	1/5	ENST00000432648.8	NP_078871.1	Q9H9L7-1
AKIRIN1	NM_001136275.2 linkuse as main transcript	c.116G>C	p.Arg39Thr	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.116G>C	p.Arg39Thr	missense_variant	1/5	1	NM_024595.3	ENSP00000392678.3	Q9H9L7-1
AKIRIN1	ENST00000446189.6 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant	1/4	2		ENSP00000389866.2	Q9H9L7-2
AKIRIN1	ENST00000372984.8 linkuse as main transcript	c.116G>C	p.Arg39Thr	missense_variant	1/4	2		ENSP00000362075.4	B4DQP0
AKIRIN1	ENST00000531822.1 linkuse as main transcript	c.-2G>C		5_prime_UTR_variant	1/4	5		ENSP00000436372.1	H0YEQ5

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000158

AC:

AN:

63292

Hom.:

AF XY:

0.00

AC XY:

AN XY:

36284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000713

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000385

AC:

AN:

1297812

Hom.:

Cov.:

AF XY:

0.00000314

AC XY:

AN XY:

637950

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000401

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:

0.00000385

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000153

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 16, 2021

The c.116G>C (p.R39T) alteration is located in exon 1 (coding exon 1) of the AKIRIN1 gene. This alteration results from a G to C substitution at nucleotide position 116, causing the arginine (R) at amino acid position 39 to be replaced by a threonine (T). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.060

T;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.68

T;T;T

M_CAP

Pathogenic

0.52

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;.

MutationTaster

Benign

0.83

D;N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.020

N;N;N

REVEL

Benign

0.054

Sift

Benign

0.30

T;T;D

Sift4G

Benign

0.57

T;T;T

Polyphen

0.23

B;.;B

Vest4

0.14

MutPred

0.34

Gain of phosphorylation at R39 (P = 9e-04);Gain of phosphorylation at R39 (P = 9e-04);Gain of phosphorylation at R39 (P = 9e-04);

MVP

0.082

MPC

0.57

ClinPred

0.12

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.20

gMVP

0.36

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