Genetic Variant NM_005098.4:c.241G>C (chr8-71843938-C-G) – 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_005098.4(MSC):c.241G>C(p.Gly81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

MSC
NM_005098.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.590

Variant links:

Genes affected

MSC (HGNC:7321): (musculin) The protein encoded by this gene is a transcriptional repressor capable of binding an E-box element either as a homodimer or as a heterodimer with E2A in vitro. The encoded protein also forms heterodimers with E2A proteins in vivo. This protein is capable of inhibiting the transactivation capability of E47, an E2A protein, in mammalian cells. This gene is a downstream target of the B-cell receptor signal transduction pathway. [provided by RefSeq, Jul 2008]

MSC links:

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

MSC-AS1 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=0.12404922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MSC	NM_005098.4 link	c.241G>C	p.Gly81Arg	missense_variant	Exon 1 of 2	ENST00000325509.5	NP_005089.2	O60682
MSC-AS1	NR_033652.1 link	n.582+234C>G		intron_variant	Intron 1 of 4
MSC-AS1	NR_033651.1 link	n.-178C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MSC	ENST00000325509.5 link	c.241G>C	p.Gly81Arg	missense_variant	Exon 1 of 2	1	NM_005098.4	ENSP00000321445.4		O60682

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.09e-7

AC:

AN:

1410988

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.19e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.073

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.35

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.13

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.28

REVEL

Benign

0.29

Sift

Benign

0.13

Sift4G

Benign

0.43

Polyphen

0.0020

Vest4

0.18

MutPred

0.41

Gain of methylation at G81 (P = 0.0023);

MVP

0.38

MPC

1.1

ClinPred

0.12

GERP RS

0.29

Varity_R

0.081

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over