Variant 3-131024651-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014065.4(ASTE1):c.656C>T(p.Ala219Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000427 in 1,594,620 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

ASTE1
NM_014065.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.44

Variant links:

Genes affected

ASTE1 (HGNC:25021): (asteroid homolog 1) Predicted to enable nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. [provided by Alliance of Genome Resources, Apr 2022]

ASTE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTE1	NM_014065.4 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	3/6	ENST00000264992.8	NP_054784.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTE1	ENST00000264992.8 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	3/6	1	NM_014065.4	ENSP00000264992	P1	Q2TB18-1
ASTE1	ENST00000514044.5 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant	3/7	1		ENSP00000426421
ASTE1	ENST00000507978.5 linkuse as main transcript	c.656C>T	p.Ala219Val	missense_variant, NMD_transcript_variant	3/7	2		ENSP00000421019		Q2TB18-2
ASTE1	ENST00000504964.1 linkuse as main transcript	c.144-413C>T		intron_variant, NMD_transcript_variant		3		ENSP00000426363

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000510

AC:

119

AN:

233454

Hom.:

AF XY:

0.000526

AC XY:

AN XY:

125446

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000994

Gnomad NFE exome

AF:

0.000843

Gnomad OTH exome

AF:

0.00160

GnomAD4 exome

AF:

0.000412

AC:

594

AN:

1442510

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

329

AN XY:

715744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000232

Gnomad4 ASJ exome

AF:

0.0000408

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00124

Gnomad4 NFE exome

AF:

0.000454

Gnomad4 OTH exome

AF:

0.000420

GnomAD4 genome

AF:

0.000572

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000841

Hom.:

Bravo

AF:

0.000450

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000643

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.045

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Uncertain

-0.097

MutationAssessor

Uncertain

2.8

.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.62

Sift

Uncertain

0.0040

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.85

MVP

0.52

MPC

0.64

ClinPred

0.20

GERP RS

4.7

Varity_R

0.44

gMVP

0.88

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