Variant chr12-6644236-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000229243.7(ACRBP):c.845T>C(p.Met282Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ACRBP
ENST00000229243.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

Variant links:

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]

ACRBP links:

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ACMG classification

Classification made for transcript

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=0.22452861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACRBP	NM_032489.3 linkuse as main transcript	c.845T>C	p.Met282Thr	missense_variant	5/10	ENST00000229243.7	NP_115878.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ACRBP	ENST00000229243.7 linkuse as main transcript	c.845T>C	p.Met282Thr	missense_variant	5/10	1	NM_032489.3	ENSP00000229243	P1
ACRBP	ENST00000414226.6 linkuse as main transcript	c.746T>C	p.Met249Thr	missense_variant	5/10	2		ENSP00000402725
ACRBP	ENST00000536350.5 linkuse as main transcript	c.845T>C	p.Met282Thr	missense_variant	5/5	2		ENSP00000443153
ACRBP	ENST00000535884.5 linkuse as main transcript			downstream_gene_variant		3		ENSP00000445262

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251438

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727182

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.845T>C (p.M282T) alteration is located in exon 5 (coding exon 5) of the ACRBP gene. This alteration results from a T to C substitution at nucleotide position 845, causing the methionine (M) at amino acid position 282 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.28

T;T;T

Eigen

Benign

-0.093

Eigen_PC

Benign

-0.036

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.63

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;.;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.18

B;B;.

Vest4

0.47

MutPred

0.35

Gain of glycosylation at M282 (P = 0.02);.;Gain of glycosylation at M282 (P = 0.02);

MVP

0.45

MPC

0.41

ClinPred

0.23

GERP RS

4.5

Varity_R

0.45

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over