dbSNP rs373641669: ACRBP:p.Ser359Ala (chr12-6643541-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032489.3(ACRBP):c.1075T>G(p.Ser359Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACRBP
NM_032489.3 missense, splice_region

Scores

Splicing: ADA: 0.00008216

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.667

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03940028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACRBP	NM_032489.3 link	c.1075T>G	p.Ser359Ala	missense_variant, splice_region_variant	Exon 6 of 10	ENST00000229243.7	NP_115878.2	Q8NEB7A0A140VJD6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACRBP	ENST00000229243.7 link	c.1075T>G	p.Ser359Ala	missense_variant, splice_region_variant	Exon 6 of 10	1	NM_032489.3	ENSP00000229243.2	Q8NEB7
ACRBP	ENST00000414226.6 link	c.976T>G	p.Ser326Ala	missense_variant, splice_region_variant	Exon 6 of 10	2		ENSP00000402725.2	E7EP66
ACRBP	ENST00000542357.1 link	n.128T>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.1

DANN

Benign

0.92

DEOGEN2

Benign

0.26

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.069

Sift

Benign

0.96

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0090

B;B

Vest4

0.28

MutPred

0.38

Gain of catalytic residue at S363 (P = 5e-04);.;

MVP

0.19

MPC

0.27

ClinPred

0.053

GERP RS

-11

Varity_R

0.055

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000082

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over