Genetic Variant MSC:p.Ala87Thr (chr8-71843920-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005098.4(MSC):c.259G>A(p.Ala87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,578,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A87S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MSC
NM_005098.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.684

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11655375).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSC	NM_005098.4	MANE Select	c.259G>A	p.Ala87Thr	missense	Exon 1 of 2	NP_005089.2	O60682
MSC-AS1	NR_033652.1		n.582+216C>T		intron	N/A
MSC-AS1	NR_033651.1		n.-196C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MSC	ENST00000325509.5	TSL:1 MANE Select	c.259G>A	p.Ala87Thr	missense	Exon 1 of 2	ENSP00000321445.4	O60682
MSC	ENST00000912144.1		c.15+244G>A		intron	N/A	ENSP00000582203.1
MSC-AS1	ENST00000521467.5	TSL:3	n.49+15705C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1426122

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

706704

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32482

American (AMR)

AF:

0.00

AC:

AN:

39962

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25432

East Asian (EAS)

AF:

0.00

AC:

AN:

37316

South Asian (SAS)

AF:

0.00

AC:

AN:

82798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5482

European-Non Finnish (NFE)

AF:

0.00000274

AC:

AN:

1096212

Other (OTH)

AF:

0.00

AC:

AN:

59038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Uncertain

0.035

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.095

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.44

M_CAP

Uncertain

0.28

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.24

MutationAssessor

Benign

1.1

PhyloP100

0.68

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.64

REVEL

Benign

0.22

Sift

Benign

0.39

Sift4G

Benign

0.55

Polyphen

0.098

Vest4

0.13

MutPred

0.33

Gain of phosphorylation at A87 (P = 0.0219)

MVP

0.42

MPC

0.76

ClinPred

0.14

GERP RS

2.1

PromoterAI

-0.060

Neutral

(source)

Varity_R

0.070

gMVP

0.21

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over