Variant 1-38998278-C-T 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.328C>T(p.His110Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000036 in 1,613,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

AKIRIN1
NM_024595.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

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=0.041263223).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AKIRIN1	NM_024595.3 linkuse as main transcript	c.328C>T	p.His110Tyr	missense_variant	2/5	ENST00000432648.8	NP_078871.1
AKIRIN1	NM_001136275.2 linkuse as main transcript	c.328C>T	p.His110Tyr	missense_variant	2/4		NP_001129747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AKIRIN1	ENST00000432648.8 linkuse as main transcript	c.328C>T	p.His110Tyr	missense_variant	2/5	1	NM_024595.3	ENSP00000392678	P1	Q9H9L7-1
AKIRIN1	ENST00000446189.6 linkuse as main transcript	c.328C>T	p.His110Tyr	missense_variant	2/4	2		ENSP00000389866		Q9H9L7-2
AKIRIN1	ENST00000531822.1 linkuse as main transcript	c.214C>T	p.His72Tyr	missense_variant	2/4	5		ENSP00000436372
AKIRIN1	ENST00000372984.8 linkuse as main transcript	c.221-2694C>T		intron_variant		2		ENSP00000362075

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

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:

0.0000479

AC:

AN:

250604

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.00

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:

0.00000881

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1460956

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

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:

0.00000720

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000164

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000601

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

Alfa

AF:

0.0000169

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

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

Jun 24, 2022

The c.328C>T (p.H110Y) alteration is located in exon 2 (coding exon 2) of the AKIRIN1 gene. This alteration results from a C to T substitution at nucleotide position 328, causing the histidine (H) at amino acid position 110 to be replaced by a tyrosine (Y). 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

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.039

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.85

D;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.9

D;N

REVEL

Benign

0.035

Sift

Benign

0.26

T;T

Sift4G

Uncertain

0.039

D;T

Polyphen

0.087

B;.

Vest4

0.26

MVP

0.068

MPC

0.49

ClinPred

0.095

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.25

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