rs5771002

Positions:

• chr22-50744827-A-C
• chr22-50744827-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001097.3(ACR):​c.886A>C​(p.Met296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: ACR NM_001097.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0759545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACR	NM_001097.3	c.886A>C	p.Met296Leu	missense_variant	5/5	ENST00000216139.10	NP_001088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACR	ENST00000216139.10	c.886A>C	p.Met296Leu	missense_variant	5/5	1	NM_001097.3	ENSP00000216139.5
ACR	ENST00000527761.1	n.345A>C		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.15
DANN	Benign	0.39
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.24	N
REVEL	Benign	0.17
Sift	Benign	0.86	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.31		Loss of MoRF binding (P = 0.084);
MVP		0.75
ClinPred		0.017	T
GERP RS		1.3
Varity_R		0.075
gMVP		0.18

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

Other links and lift over

dbSNP: rs5771002; hg19: chr22-51183255;