Variant 1-38991552-C-G 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_024595.3(AKIRIN1):c.172C>G(p.Leu58Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000574 in 1,410,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

AKIRIN1
NM_024595.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.14

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=0.05785227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIRIN1	NM_024595.3 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	1/5	ENST00000432648.8	NP_078871.1
AKIRIN1	NM_001136275.2 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	1/4		NP_001129747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKIRIN1	ENST00000432648.8 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	1/5	1	NM_024595.3	ENSP00000392678	P1	Q9H9L7-1
AKIRIN1	ENST00000446189.6 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	1/4	2		ENSP00000389866		Q9H9L7-2
AKIRIN1	ENST00000372984.8 linkuse as main transcript	c.172C>G	p.Leu58Val	missense_variant	1/4	2		ENSP00000362075
AKIRIN1	ENST00000531822.1 linkuse as main transcript	c.58C>G	p.Leu20Val	missense_variant	1/4	5		ENSP00000436372

Frequencies

GnomAD3 genomes

AF:

0.000290

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000357

AC:

AN:

56060

Hom.:

AF XY:

0.00

AC XY:

AN XY:

33604

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000216

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:

0.0000246

AC:

AN:

1258370

Hom.:

Cov.:

AF XY:

0.0000260

AC XY:

AN XY:

616444

show subpopulations

Gnomad4 AFR exome

AF:

0.000784

Gnomad4 AMR exome

AF:

0.000107

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:

0.00000295

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000329

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00120

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000261

ExAC

AF:

0.0000404

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

Dec 07, 2021

The c.172C>G (p.L58V) alteration is located in exon 1 (coding exon 1) of the AKIRIN1 gene. This alteration results from a C to G substitution at nucleotide position 172, causing the leucine (L) at amino acid position 58 to be replaced by a valine (V). 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

0.060

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.20

T;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.66

T;T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.95

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.59

T;T;T

Polyphen

0.018

B;.;B

Vest4

0.091

MVP

0.17

MPC

0.47

ClinPred

0.058

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.044

gMVP

0.23

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