Variant 3-131024583-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014065.4(ASTE1):c.724C>A(p.Pro242Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,613,222 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 2 hom. )

Consequence

ASTE1
NM_014065.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.414

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004839897).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASTE1	NM_014065.4 linkuse as main transcript	c.724C>A	p.Pro242Thr	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.724C>A	p.Pro242Thr	missense_variant	3/6	1	NM_014065.4	ENSP00000264992	P1	Q2TB18-1
ASTE1	ENST00000514044.5 linkuse as main transcript	c.724C>A	p.Pro242Thr	missense_variant	3/7	1		ENSP00000426421
ASTE1	ENST00000507978.5 linkuse as main transcript	c.724C>A	p.Pro242Thr	missense_variant, NMD_transcript_variant	3/7	2		ENSP00000421019		Q2TB18-2
ASTE1	ENST00000504964.1 linkuse as main transcript	c.144-345C>A		intron_variant, NMD_transcript_variant		3		ENSP00000426363

Frequencies

GnomAD3 genomes

AF:

0.000368

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000515

AC:

129

AN:

250680

Hom.:

AF XY:

0.000620

AC XY:

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00920

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000272

AC:

397

AN:

1460976

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

205

AN XY:

726788

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000269

Gnomad4 ASJ exome

AF:

0.00920

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000855

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000361

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000504

Hom.:

Bravo

AF:

0.000400

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000428

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

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 11, 2021

The c.724C>A (p.P242T) alteration is located in exon 3 (coding exon 1) of the ASTE1 gene. This alteration results from a C to A substitution at nucleotide position 724, causing the proline (P) at amino acid position 242 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

Benign

0.095

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.083

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.049

D;T

Polyphen

0.85

P;P

Vest4

0.13

MVP

0.40

MPC

0.62

ClinPred

0.11

GERP RS

2.4

Varity_R

0.11

gMVP

0.34

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