rs10994385

Positions:

• chr10-46038901-C-G
• chr10-46038901-C-T

Variant summary

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

The ENST00000582163.3(MSMB):​c.215+65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,372,806 control chromosomes in the GnomAD database, including 26,674 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 0.26 (6247 hom., cov: 32)
  • Exomes 𝑓: 0.18 (20427 hom.)
• Consequence: MSMB ENST00000582163.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.463

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSMB	NM_002443.4	c.215+65G>C		intron_variant		ENST00000582163.3	NP_002434.1
MSMB	NM_138634.3	c.109+1085G>C		intron_variant			NP_619540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMB	ENST00000582163.3	c.215+65G>C		intron_variant		1	NM_002443.4	ENSP00000463092	P1
MSMB	ENST00000581478.5	c.109+1085G>C		intron_variant		1		ENSP00000462641
MSMB	ENST00000663171.1	c.215+65G>C		intron_variant				ENSP00000499419

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38902 AN: 151956 Hom.: 6242 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.175 AC: 214006 AN: 1220732 Hom.: 20427 AF XY: 0.174 AC XY: 107218 AN XY: 616348

Gnomad4 AFR exome AF: 0.473

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.256 AC: 38944 AN: 152074 Hom.: 6247 Cov.: 32 AF XY: 0.252 AC XY: 18739 AN XY: 74334

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.240

Alfa AF: 0.0833 Hom.: 101

Bravo AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.46
DANN	Benign	0.39

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: rs10994385; hg19: chr10-51556921;