rs10993994

Variant names:

• chr10-46046326-A-G
• rs10993994
• ENST00000663171.1:c.-89T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000663171.1(MSMB):​c.-89T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,161,688 control chromosomes in the GnomAD database, including 200,462 homozygotes. 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: 𝑓 0.54 (22862 hom., cov: 33)
  • Exomes 𝑓: 0.59 (177600 hom.)
• Consequence: MSMB ENST00000663171.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

MSMB (HGNC:7372): (microseminoprotein beta) The protein encoded by this gene is a member of the immunoglobulin binding factor family. It is synthesized by the epithelial cells of the prostate gland and secreted into the seminal plasma. This protein has inhibin-like activity. It may have a role as an autocrine paracrine factor in uterine, breast and other female reproductive tissues. The expression of the encoded protein is found to be decreased in prostate cancer. Two alternatively spliced transcript variants encoding different isoforms are described for this gene. The use of alternate polyadenylation sites has been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSMB	NM_002443.4	c.-89T>C		upstream_gene_variant		ENST00000582163.3	NP_002434.1
MSMB	NM_138634.3	c.-89T>C		upstream_gene_variant			NP_619540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSMB	ENST00000663171.1	c.-89T>C		5_prime_UTR_variant	Exon 2 of 5			ENSP00000499419.1
MSMB	ENST00000582163.3	c.-89T>C		upstream_gene_variant		1	NM_002443.4	ENSP00000463092.1
MSMB	ENST00000581478.5	c.-89T>C		upstream_gene_variant		1		ENSP00000462641.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81774 AN: 151992 Hom.: 22866 Cov.: 33

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.646

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.535

GnomAD4 exome AF: 0.587 AC: 593099 AN: 1009578 Hom.: 177600 AF XY: 0.580 AC XY: 302844 AN XY: 521818

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.650

Gnomad4 NFE exome AF: 0.612

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.538 AC: 81778 AN: 152110 Hom.: 22862 Cov.: 33 AF XY: 0.536 AC XY: 39875 AN XY: 74348

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.539

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.646

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.529

Alfa AF: 0.584 Hom.: 52172

Bravo AF: 0.534

Asia WGS AF: 0.435 AC: 1513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10993994; hg19: chr10-51549496;