dbSNP rs183967306: ASTL:p.Pro304Pro (chr2-96124234-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001002036.4(ASTL):c.912G>A(p.Pro304Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00575 in 1,514,630 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 40 hom. )

Consequence

ASTL
NM_001002036.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.68

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-96124234-C-T is Benign according to our data. Variant chr2-96124234-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2651138.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.68 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

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.912G>A	p.Pro304Pro	synonymous	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.912G>A	p.Pro304Pro	synonymous	Exon 9 of 9	ENSP00000343674.2	Q6HA08
	ASTL	ENST00000867255.1		c.858G>A	p.Pro286Pro	synonymous	Exon 9 of 9	ENSP00000537314.1

Frequencies

GnomAD3 genomes

AF:

0.00485

AC:

737

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00656

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00535

AC:

904

AN:

168838

AF XY:

0.00554

show subpopulations

Gnomad AFR exome

AF:

0.000961

Gnomad AMR exome

AF:

0.00890

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00122

Gnomad NFE exome

AF:

0.00718

Gnomad OTH exome

AF:

0.00836

GnomAD4 exome

AF:

0.00585

AC:

7970

AN:

1362438

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

3824

AN XY:

667084

show subpopulations

African (AFR)

AF:

0.000894

AC:

AN:

30194

American (AMR)

AF:

0.00949

AC:

274

AN:

28886

Ashkenazi Jewish (ASJ)

AF:

0.00943

AC:

187

AN:

19822

East Asian (EAS)

AF:

0.00

AC:

AN:

38794

South Asian (SAS)

AF:

0.00167

AC:

117

AN:

69968

European-Finnish (FIN)

AF:

0.00166

AC:

AN:

48674

Middle Eastern (MID)

AF:

0.00394

AC:

AN:

5076

European-Non Finnish (NFE)

AF:

0.00652

AC:

6948

AN:

1065030

Other (OTH)

AF:

0.00564

AC:

316

AN:

55994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

432

863

1295

1726

2158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.00484

AC:

736

AN:

152192

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

375

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

41522

American (AMR)

AF:

0.0107

AC:

163

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00923

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.00166

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00656

AC:

446

AN:

67988

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

113

151

189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00502

Hom.:

Bravo

AF:

0.00544

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.71

(source)

DANN

Benign

0.60

PhyloP100

-1.7

Mutation Taster

=100/0

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