22-50744827-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001097.3(ACR):c.886A>G(p.Met296Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 1,600,480 control chromosomes in the GnomAD database, including 374,742 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M296I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.68 ( 34480 hom., cov: 22)

Exomes 𝑓: 0.68 ( 340262 hom. )

Consequence

ACR
NM_001097.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.457

Publications

16 publications found

Variant links:

Genes affected

ACR (HGNC:126): (acrosin) Acrosin is the major proteinase present in the acrosome of mature spermatozoa. It is a typical serine proteinase with trypsin-like specificity. It is stored in the acrosome in its precursor form, proacrosin. The active enzyme functions in the lysis of the zona pellucida, thus facilitating penetration of the sperm through the innermost glycoprotein layers of the ovum. The mRNA for proacrosin is synthesized only in the postmeiotic stages of spermatogenesis. In humans proacrosin first appears in the haploid spermatids. [provided by RefSeq, Jul 2008]

ACR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2673811E-6).

BP6

Variant 22-50744827-A-G is Benign according to our data. Variant chr22-50744827-A-G is described in ClinVar as Benign. ClinVar VariationId is 402336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACR	NM_001097.3 link	c.886A>G	p.Met296Val	missense_variant	Exon 5 of 5	ENST00000216139.10	NP_001088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACR	ENST00000216139.10 link	c.886A>G	p.Met296Val	missense_variant	Exon 5 of 5	1	NM_001097.3	ENSP00000216139.5
ACR	ENST00000527761.1 link	n.345A>G		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

100960

AN:

148446

Hom.:

34452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.763

Gnomad AMR

AF:

0.689

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.812

Gnomad SAS

AF:

0.804

Gnomad FIN

AF:

0.712

Gnomad MID

AF:

0.653

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.651

GnomAD2 exomes

AF:

0.712

AC:

136773

AN:

192086

AF XY:

0.715

show subpopulations

Gnomad AFR exome

AF:

0.667

Gnomad AMR exome

AF:

0.730

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.806

Gnomad FIN exome

AF:

0.713

Gnomad NFE exome

AF:

0.664

Gnomad OTH exome

AF:

0.700

GnomAD4 exome

AF:

0.683

AC:

991752

AN:

1451922

Hom.:

340262

Cov.:

AF XY:

0.687

AC XY:

495550

AN XY:

721412

show subpopulations

African (AFR)

AF:

0.667

AC:

22066

AN:

33086

American (AMR)

AF:

0.729

AC:

31852

AN:

43672

Ashkenazi Jewish (ASJ)

AF:

0.740

AC:

19179

AN:

25910

East Asian (EAS)

AF:

0.832

AC:

32549

AN:

39124

South Asian (SAS)

AF:

0.806

AC:

68382

AN:

84878

European-Finnish (FIN)

AF:

0.711

AC:

37246

AN:

52368

Middle Eastern (MID)

AF:

0.690

AC:

3974

AN:

5756

European-Non Finnish (NFE)

AF:

0.664

AC:

735309

AN:

1107134

Other (OTH)

AF:

0.687

AC:

41195

AN:

59994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

17606

35212

52817

70423

88029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19238

38476

57714

76952

96190

<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:

0.680

AC:

101030

AN:

148558

Hom.:

34480

Cov.:

AF XY:

0.683

AC XY:

49361

AN XY:

72304

show subpopulations

African (AFR)

AF:

0.663

AC:

26659

AN:

40200

American (AMR)

AF:

0.689

AC:

10371

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2501

AN:

3444

East Asian (EAS)

AF:

0.812

AC:

3869

AN:

4766

South Asian (SAS)

AF:

0.803

AC:

3682

AN:

4586

European-Finnish (FIN)

AF:

0.712

AC:

7257

AN:

10194

Middle Eastern (MID)

AF:

0.647

AC:

189

AN:

292

European-Non Finnish (NFE)

AF:

0.663

AC:

44488

AN:

67070

Other (OTH)

AF:

0.646

AC:

1330

AN:

2058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

798

1596

2394

3192

3990

<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:

0.674

Hom.:

5909

Bravo

AF:

0.679

ExAC

AF:

0.682

AC:

80091

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 73% of total chromosomes in ExAC

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

0.34

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.23

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

PhyloP100

-0.46

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.64

REVEL

Benign

0.16

Sift

Benign

0.11

Sift4G

Benign

0.31

Vest4

0.053

ClinPred

0.011

GERP RS

1.3

Varity_R

0.073

gMVP

0.23

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over