rs3791783

chr2-190059437-T-C

Variant summary

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

The NM_005259.3(MSTN):c.747+625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,798 control chromosomes in the GnomAD database, including 13,305 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 0.35 (13305 hom., cov: 32)
• Consequence: MSTN NM_005259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

Genes affected

MSTN (HGNC:4223): (myostatin) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. This protein negatively regulates skeletal muscle cell proliferation and differentiation. Mutations in this gene are associated with increased skeletal muscle mass in humans and other mammals. [provided by RefSeq, Jul 2016]

C2orf88 (HGNC:28191): (chromosome 2 open reading frame 88) Predicted to enable protein kinase A regulatory subunit binding activity. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MSTN	NM_005259.3	c.747+625A>G		intron_variant		ENST00000260950.5
C2orf88	XM_047446008.1	c.-517-20517T>C		intron_variant
C2orf88	XM_047446009.1	c.-517-20517T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MSTN	ENST00000260950.5	c.747+625A>G		intron_variant		1	NM_005259.3	P1
C2orf88	ENST00000478197.1	n.220-19786T>C		intron_variant, non_coding_transcript_variant		4
C2orf88	ENST00000495546.1	n.202-20517T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52998 AN: 151680 Hom.: 13252 Cov.: 32

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.341

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.350 AC: 53112 AN: 151798 Hom.: 13305 Cov.: 32 AF XY: 0.341 AC XY: 25316 AN XY: 74212

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.341

Alfa AF: 0.291 Hom.: 1155

Bravo AF: 0.379

Asia WGS AF: 0.249 AC: 866 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.67
Dann	Benign	0.72

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: rs3791783; hg19: chr2-190924163;