NM_032489.3:c.958C>G

Variant names:

• chr12-6643658-G-C
• rs763689381
• NM_032489.3:c.958C>G

Variant summary

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

The NM_032489.3(ACRBP):​c.958C>G​(p.Pro320Ala) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACRBP NM_032489.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.24

Genes affected

ACRBP (HGNC:17195): (acrosin binding protein) The protein encoded by this gene is similar to proacrosin binding protein sp32 precursor found in mouse, guinea pig, and pig. This protein is located in the sperm acrosome and is thought to function as a binding protein to proacrosin for packaging and condensation of the acrosin zymogen in the acrosomal matrix. This protein is a member of the cancer/testis family of antigens and it is found to be immunogenic. In normal tissues, this mRNA is expressed only in testis, whereas it is detected in a range of different tumor types such as bladder, breast, lung, liver, and colon. [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=0.22580704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACRBP	NM_032489.3	c.958C>G	p.Pro320Ala	missense_variant	Exon 6 of 10	ENST00000229243.7	NP_115878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACRBP	ENST00000229243.7	c.958C>G	p.Pro320Ala	missense_variant	Exon 6 of 10	1	NM_032489.3	ENSP00000229243.2
ACRBP	ENST00000414226.6	c.859C>G	p.Pro287Ala	missense_variant	Exon 6 of 10	2		ENSP00000402725.2
ACRBP	ENST00000542357.1	n.11C>G		non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.1	D;D
REVEL	Benign	0.11
Sift	Uncertain	0.027	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.15	B;B
Vest4		0.36
MutPred		0.61		Gain of catalytic residue at E323 (P = 0.0173);.;
MVP		0.53
MPC		0.56
ClinPred		0.78	D
GERP RS		3.5
Varity_R		0.10
gMVP		0.16

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: rs763689381; hg19: chr12-6752824;