Genetic Variant MSC:p.Gly85Ser (chr8-71843926-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_005098.4(MSC):c.253G>A(p.Gly85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000573 in 1,571,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

MSC
NM_005098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.176

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 8 AD gene.

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.253G>A	p.Gly85Ser	missense	Exon 1 of 2	NP_005089.2	O60682
MSC-AS1	NR_033652.1		n.582+222C>T		intron	N/A
MSC-AS1	NR_033651.1		n.-190C>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.253G>A	p.Gly85Ser	missense	Exon 1 of 2	ENSP00000321445.4	O60682
MSC	ENST00000912144.1		c.15+238G>A		intron	N/A	ENSP00000582203.1
MSC-AS1	ENST00000521467.5	TSL:3	n.49+15711C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152230

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

170448

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000564

AC:

AN:

1418790

Hom.:

Cov.:

AF XY:

0.00000569

AC XY:

AN XY:

702466

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32256

American (AMR)

AF:

0.00

AC:

AN:

38900

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25346

East Asian (EAS)

AF:

0.000190

AC:

AN:

36850

South Asian (SAS)

AF:

0.00

AC:

AN:

82104

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1092538

Other (OTH)

AF:

0.00

AC:

AN:

58752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Uncertain

0.085

BayesDel_noAF

Benign

-0.12

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.13

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.11

MetaSVM

Uncertain

0.61

MutationAssessor

Benign

1.0

PhyloP100

0.18

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.24

REVEL

Benign

0.28

Sift

Benign

0.062

Sift4G

Benign

0.14

Polyphen

0.41

Vest4

0.16

MutPred

0.21

Gain of phosphorylation at G85 (P = 0.0051)

MVP

0.38

MPC

0.79

ClinPred

0.14

GERP RS

3.0

PromoterAI

-0.0075

Neutral

(source)

Varity_R

0.11

gMVP

0.23

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over