NM_005259.3:c.747+625A>G

Variant names:

• chr2-190059437-T-C
• rs3791783
• NM_005259.3:c.747+625A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MSTN	NM_005259.3	c.747+625A>G		intron_variant	Intron 2 of 2	ENST00000260950.5	NP_005250.1
AKAP19	XM_047446008.1	c.-517-20517T>C		intron_variant	Intron 2 of 6		XP_047301964.1
AKAP19	XM_047446009.1	c.-517-20517T>C		intron_variant	Intron 1 of 5		XP_047301965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSTN	ENST00000260950.5	c.747+625A>G		intron_variant	Intron 2 of 2	1	NM_005259.3	ENSP00000260950.3
C2orf88	ENST00000478197.1	n.220-19786T>C		intron_variant	Intron 1 of 1	4
C2orf88	ENST00000495546.1	n.202-20517T>C		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.714 AC: 29586 AN: 41410

American (AMR) AF: 0.266 AC: 4045 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3460

East Asian (EAS) AF: 0.257 AC: 1328 AN: 5164

South Asian (SAS) AF: 0.169 AC: 816 AN: 4822

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10588

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.205 AC: 13934 AN: 67836

Other (OTH) AF: 0.341 AC: 717 AN: 2100

Alfa AF: 0.307 Hom.: 1339

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
PhyloP100		-1.8
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3791783; hg19: chr2-190924163;