ENST00000663171.1:c.-52T>G

Variant names:

• chr10-46046289-A-C
• rs41274660
• ENST00000663171.1:c.-52T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000663171.1(MSMB):​c.-52T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,579,506 control chromosomes in the GnomAD database, including 99 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 0.0076 (6 hom., cov: 34)
  • Exomes 𝑓: 0.011 (93 hom.)
• Consequence: MSMB ENST00000663171.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000663171.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMB	NM_002443.4	MANE Select	c.-52T>G		upstream_gene	N/A	NP_002434.1	P08118-1
	MSMB	NM_138634.3		c.-52T>G		upstream_gene	N/A	NP_619540.1	P08118-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSMB	ENST00000663171.1		c.-52T>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000499419.1	A0A590UJG9
	MSMB	ENST00000663171.1		c.-52T>G		5_prime_UTR	Exon 2 of 5	ENSP00000499419.1	A0A590UJG9
	MSMB	ENST00000582163.3	TSL:1 MANE Select	c.-52T>G		upstream_gene	N/A	ENSP00000463092.1	P08118-1

Frequencies

GnomAD3 genomes AF: 0.00759 AC: 1155 AN: 152232 Hom.: 6 Cov.: 34

Gnomad AFR AF: 0.00265

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00550

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.00766

GnomAD4 exome AF: 0.0111 AC: 15859 AN: 1427156 Hom.: 93 Cov.: 26 AF XY: 0.0108 AC XY: 7696 AN XY: 712332

African (AFR) AF: 0.00158 AC: 52 AN: 32872

American (AMR) AF: 0.00645 AC: 287 AN: 44498

Ashkenazi Jewish (ASJ) AF: 0.0189 AC: 489 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39500

South Asian (SAS) AF: 0.00171 AC: 146 AN: 85258

European-Finnish (FIN) AF: 0.00611 AC: 326 AN: 53386

Middle Eastern (MID) AF: 0.00367 AC: 21 AN: 5716

European-Non Finnish (NFE) AF: 0.0129 AC: 13932 AN: 1080816

Other (OTH) AF: 0.0102 AC: 606 AN: 59226

GnomAD4 genome AF: 0.00758 AC: 1155 AN: 152350 Hom.: 6 Cov.: 34 AF XY: 0.00701 AC XY: 522 AN XY: 74502

African (AFR) AF: 0.00264 AC: 110 AN: 41594

American (AMR) AF: 0.00549 AC: 84 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00358 AC: 38 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0121 AC: 825 AN: 68036

Other (OTH) AF: 0.00758 AC: 16 AN: 2112

Alfa AF: 0.0119 Hom.: 17

Bravo AF: 0.00829

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.81
PhyloP100		-0.59
PromoterAI		0.025	Neutral

Splicing

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

Other links and lift over

dbSNP: rs41274660; hg19: chr10-51549533;