rs11681628

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005259.3(MSTN):​c.747+701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 151,664 control chromosomes in the GnomAD database, including 1,425 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 0.12 ( 1425 hom., cov: 32)

Consequence

MSTN
NM_005259.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.26
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MSTNNM_005259.3 linkuse as main transcriptc.747+701C>T intron_variant ENST00000260950.5 NP_005250.1
C2orf88XM_047446008.1 linkuse as main transcriptc.-517-20593G>A intron_variant XP_047301964.1
C2orf88XM_047446009.1 linkuse as main transcriptc.-517-20593G>A intron_variant XP_047301965.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MSTNENST00000260950.5 linkuse as main transcriptc.747+701C>T intron_variant 1 NM_005259.3 ENSP00000260950 P1
C2orf88ENST00000478197.1 linkuse as main transcriptn.220-19862G>A intron_variant, non_coding_transcript_variant 4
C2orf88ENST00000495546.1 linkuse as main transcriptn.202-20593G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.121
AC:
18339
AN:
151546
Hom.:
1425
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0348
Gnomad AMI
AF:
0.0888
Gnomad AMR
AF:
0.115
Gnomad ASJ
AF:
0.185
Gnomad EAS
AF:
0.0206
Gnomad SAS
AF:
0.121
Gnomad FIN
AF:
0.133
Gnomad MID
AF:
0.223
Gnomad NFE
AF:
0.177
Gnomad OTH
AF:
0.131
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.121
AC:
18337
AN:
151664
Hom.:
1425
Cov.:
32
AF XY:
0.118
AC XY:
8760
AN XY:
74128
show subpopulations
Gnomad4 AFR
AF:
0.0347
Gnomad4 AMR
AF:
0.115
Gnomad4 ASJ
AF:
0.185
Gnomad4 EAS
AF:
0.0206
Gnomad4 SAS
AF:
0.121
Gnomad4 FIN
AF:
0.133
Gnomad4 NFE
AF:
0.177
Gnomad4 OTH
AF:
0.134
Alfa
AF:
0.145
Hom.:
244
Bravo
AF:
0.114
Asia WGS
AF:
0.100
AC:
346
AN:
3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
14
DANN
Benign
0.41

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11681628; hg19: chr2-190924087; API