dbSNP rs750451671: ASTL:p.Lys352Arg (chr2-96124091-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001002036.4(ASTL):c.1055A>G(p.Lys352Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,610,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ASTL
NM_001002036.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.351

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013020694).

BP6

Variant 2-96124091-T-C is Benign according to our data. Variant chr2-96124091-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3319047.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002036.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTL	NM_001002036.4	MANE Select	c.1055A>G	p.Lys352Arg	missense	Exon 9 of 9	NP_001002036.3	Q6HA08

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASTL	ENST00000342380.3	TSL:1 MANE Select	c.1055A>G	p.Lys352Arg	missense	Exon 9 of 9	ENSP00000343674.2	Q6HA08
	ASTL	ENST00000867255.1		c.1001A>G	p.Lys334Arg	missense	Exon 9 of 9	ENSP00000537314.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD2 exomes

AF:

0.0000765

AC:

AN:

248362

AF XY:

0.0000670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000524

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1458430

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33418

American (AMR)

AF:

0.000449

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25922

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52926

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109958

Other (OTH)

AF:

0.0000166

AC:

AN:

60224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000311

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000123

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.4

(source)

DANN

Benign

0.089

DEOGEN2

Benign

0.00047

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.37

M_CAP

Benign

0.0086

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

PhyloP100

-0.35

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.12

REVEL

Benign

0.057

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.015

MutPred

0.089

Loss of ubiquitination at K352 (P = 0.0051)

MVP

0.25

MPC

0.11

ClinPred

0.015

GERP RS

0.67

Varity_R

0.029

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over