Variant 1-38991514-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024595.3(AKIRIN1):c.134C>T(p.Pro45Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,299,236 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: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

AKIRIN1
NM_024595.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.844

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:

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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=0.20121932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIRIN1	NM_024595.3 linkuse as main transcript	c.134C>T	p.Pro45Leu	missense_variant	1/5	ENST00000432648.8	NP_078871.1
AKIRIN1	NM_001136275.2 linkuse as main transcript	c.134C>T	p.Pro45Leu	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.134C>T	p.Pro45Leu	missense_variant	1/5	1	NM_024595.3	ENSP00000392678	P1	Q9H9L7-1
AKIRIN1	ENST00000446189.6 linkuse as main transcript	c.134C>T	p.Pro45Leu	missense_variant	1/4	2		ENSP00000389866		Q9H9L7-2
AKIRIN1	ENST00000372984.8 linkuse as main transcript	c.134C>T	p.Pro45Leu	missense_variant	1/4	2		ENSP00000362075
AKIRIN1	ENST00000531822.1 linkuse as main transcript	c.20C>T	p.Pro7Leu	missense_variant	1/4	5		ENSP00000436372

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000154

AC:

AN:

1299236

Hom.:

Cov.:

AF XY:

0.00000157

AC XY:

AN XY:

638768

show subpopulations

Gnomad4 AFR exome

AF:

0.0000751

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 24, 2024

The c.134C>T (p.P45L) alteration is located in exon 1 (coding exon 1) of the AKIRIN1 gene. This alteration results from a C to T substitution at nucleotide position 134, causing the proline (P) at amino acid position 45 to be replaced by a leucine (L). 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

0.069

BayesDel_addAF

Benign

-0.078

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

T;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.87

D;D;T

M_CAP

Pathogenic

0.51

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.055

N;N;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.84

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.069

T;T;T

Sift4G

Benign

0.098

T;T;T

Polyphen

0.023

B;.;D

Vest4

0.27

MutPred

0.29

Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);Loss of relative solvent accessibility (P = 0.0186);

MVP

0.23

MPC

0.34

ClinPred

0.85

GERP RS

2.6

Varity_R

0.11

gMVP

0.28

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