dbSNP rs201235770: MYOD1:p.Arg41His (chr11-17719904-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002478.5(MYOD1):c.122G>A(p.Arg41His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R41L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Consequence

MYOD1
NM_002478.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.58

Variant links:

Genes affected

MYOD1 (HGNC:7611): (myogenic differentiation 1) This gene encodes a nuclear protein that belongs to the basic helix-loop-helix family of transcription factors and the myogenic factors subfamily. It regulates muscle cell differentiation by inducing cell cycle arrest, a prerequisite for myogenic initiation. The protein is also involved in muscle regeneration. It activates its own transcription which may stabilize commitment to myogenesis. [provided by RefSeq, Jul 2008]

MYOD1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20559159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOD1	NM_002478.5 link	c.122G>A	p.Arg41His	missense_variant	Exon 1 of 3	ENST00000250003.4	NP_002469.2	P15172

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOD1	ENST00000250003.4 link	c.122G>A	p.Arg41His	missense_variant	Exon 1 of 3	1	NM_002478.5	ENSP00000250003.3		P15172

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250904

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.35

Eigen

Benign

-0.26

Eigen_PC

Benign

0.010

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.018

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-0.90

PrimateAI

Benign

0.42

PROVEAN

Benign

0.96

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

0.60

Polyphen

0.037

Vest4

0.20

MutPred

0.45

Gain of glycosylation at S37 (P = 0.1207);

MVP

0.66

MPC

1.5

ClinPred

0.77

GERP RS

5.2

Varity_R

0.072

gMVP

0.38

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over