22-50738306-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001097.3(ACR):c.71C>T(p.Thr24Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000836 in 1,613,834 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00065 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00086 (17 hom.)
• Consequence: ACR NM_001097.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013070911).
• BP6: Variant 22-50738306-C-T is Benign according to our data. Variant chr22-50738306-C-T is described in ClinVar as [Benign]. Clinvar id is 727057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000855 (1250/1461650) while in subpopulation EAS AF= 0.0284 (1129/39700). AF 95% confidence interval is 0.0271. There are 17 homozygotes in gnomad4_exome. There are 576 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACR	NM_001097.3	c.71C>T	p.Thr24Met	missense_variant	1/5	ENST00000216139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACR	ENST00000216139.10	c.71C>T	p.Thr24Met	missense_variant	1/5	1	NM_001097.3	P1
ACR	ENST00000533930.1	n.111C>T		non_coding_transcript_exon_variant	1/3	1
ACR	ENST00000529621.1	c.71C>T	p.Thr24Met	missense_variant	1/4	5

Frequencies

GnomAD3 genomes AF: 0.000651 AC: 99 AN: 152066 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0164

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00166 AC: 416 AN: 251250 Hom.: 7 AF XY: 0.00149 AC XY: 203 AN XY: 135810

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0213

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000855 AC: 1250 AN: 1461650 Hom.: 17 Cov.: 31 AF XY: 0.000792 AC XY: 576 AN XY: 727146

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0284

Gnomad4 SAS exome AF: 0.000301

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.000861

GnomAD4 genome AF: 0.000651 AC: 99 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74416

Gnomad4 AFR AF: 0.0000964

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00132 Hom.: 3

Bravo AF: 0.00102

ExAC AF: 0.00158 AC: 192

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Uncertain	0.030
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.87	D
MetaRNN	Benign	0.013	T;T
MetaSVM	Uncertain	0.41	D
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	0.64	N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		1.0	D;D
Vest4		0.51
MVP		0.96
ClinPred		0.022	T
GERP RS		4.0
Varity_R		0.065
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs79314756; hg19: chr22-51176734;