Variant chr2-96132567-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000342380.3(ASTL):c.610C>T(p.Arg204Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00331 in 1,607,616 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R204H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 10 hom. )

Consequence

ASTL
ENST00000342380.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.717

Variant links:

Genes affected

ASTL (HGNC:31704): (astacin like metalloendopeptidase) Predicted to enable aspartic-type peptidase activity; glutamic-type peptidase activity; and metalloendopeptidase activity. Predicted to be involved in several processes, including negative regulation of binding activity of sperm to zona pellucida; positive regulation of protein processing; and prevention of polyspermy. Predicted to be located in cortical granule and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ASTL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033493906).

BP6

Variant 2-96132567-G-A is Benign according to our data. Variant chr2-96132567-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651139.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ASTL	NM_001002036.4 linkuse as main transcript	c.610C>T	p.Arg204Cys	missense_variant	6/9	ENST00000342380.3	NP_001002036.3
ASTL	XM_011511205.3 linkuse as main transcript	c.625C>T	p.Arg209Cys	missense_variant	5/8		XP_011509507.1
ASTL	XM_011511207.3 linkuse as main transcript	c.625C>T	p.Arg209Cys	missense_variant	5/8		XP_011509509.1
ASTL	XM_011511208.3 linkuse as main transcript	c.625C>T	p.Arg209Cys	missense_variant	5/7		XP_011509510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASTL	ENST00000342380.3 linkuse as main transcript	c.610C>T	p.Arg204Cys	missense_variant	6/9	1	NM_001002036.4	ENSP00000343674	P1

Frequencies

GnomAD3 genomes

AF:

0.00269

AC:

409

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00448

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00252

AC:

628

AN:

249666

Hom.:

AF XY:

0.00249

AC XY:

337

AN XY:

135106

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00550

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00419

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00337

AC:

4911

AN:

1455308

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

2330

AN XY:

722842

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00496

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.00283

Gnomad4 NFE exome

AF:

0.00399

Gnomad4 OTH exome

AF:

0.00231

GnomAD4 genome

AF:

0.00269

AC:

409

AN:

152308

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

188

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00448

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00396

Hom.:

Bravo

AF:

0.00238

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00229

AC:

278

EpiCase

AF:

0.00284

EpiControl

AF:

0.00351

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

ASTL: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.033

MetaSVM

Benign

-0.79

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.29

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0090

Polyphen

0.99

Vest4

0.60

MVP

0.82

MPC

0.65

ClinPred

0.064

GERP RS

3.2

Varity_R

0.41

gMVP

0.82

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