rs1064733

Variant names:

• chr22-50739384-C-G
• rs1064733
• NM_001097.3:c.191C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-50739384-C-G
• chr22-50739384-C-T

Variant summary

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

The NM_001097.3(ACR):​c.191C>G​(p.Thr64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ACR NM_001097.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACR	NM_001097.3	c.191C>G	p.Thr64Arg	missense_variant	Exon 2 of 5	ENST00000216139.10	NP_001088.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACR	ENST00000216139.10	c.191C>G	p.Thr64Arg	missense_variant	Exon 2 of 5	1	NM_001097.3	ENSP00000216139.5
ACR	ENST00000533930.1	n.231C>G		non_coding_transcript_exon_variant	Exon 2 of 3	1
ACR	ENST00000529621.1	c.191C>G	p.Thr64Arg	missense_variant	Exon 2 of 4	5		ENSP00000435120.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461670 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.79
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.027	N
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.28	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.41
Sift	Benign	0.25	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.79	P;P
Vest4		0.17
MutPred		0.60		Gain of MoRF binding (P = 0.0109);Gain of MoRF binding (P = 0.0109);
MVP		0.83
ClinPred		0.37	T
GERP RS		-2.7
Varity_R		0.11
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.49		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.49		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1064733; hg19: chr22-51177812;