Variant 8-71843920-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005098.4(MSC):c.259G>T(p.Ala87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,578,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

MSC
NM_005098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.684

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03772673).

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSC	NM_005098.4 linkuse as main transcript	c.259G>T	p.Ala87Ser	missense_variant	1/2	ENST00000325509.5	NP_005089.2
MSC-AS1	NR_033652.1 linkuse as main transcript	n.582+216C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MSC	ENST00000325509.5 linkuse as main transcript	c.259G>T	p.Ala87Ser	missense_variant	1/2	1	NM_005098.4	ENSP00000321445	P1
MSC-AS1	ENST00000521467.5 linkuse as main transcript	n.49+15705C>A		intron_variant, non_coding_transcript_variant		3
MSC-AS1	ENST00000522519.5 linkuse as main transcript	n.582+216C>A		intron_variant, non_coding_transcript_variant		2
MSC-AS1	ENST00000524152.5 linkuse as main transcript	n.144+216C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000105

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:

0.000235

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000123

AC:

AN:

179498

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

98780

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:

0.000282

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.000274

AC:

391

AN:

1426122

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

186

AN XY:

706704

show subpopulations

Gnomad4 AFR exome

AF:

0.0000616

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:

0.0000422

Gnomad4 NFE exome

AF:

0.000332

Gnomad4 OTH exome

AF:

0.000390

GnomAD4 genome

AF:

0.000105

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000247

AC:

ExAC

AF:

0.0000950

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.259G>T (p.A87S) alteration is located in exon 1 (coding exon 1) of the MSC gene. This alteration results from a G to T substitution at nucleotide position 259, causing the alanine (A) at amino acid position 87 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.19

CADD

Benign

5.4

DANN

Benign

0.78

DEOGEN2

Benign

0.076

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.38

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.038

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.13

REVEL

Benign

0.25

Sift

Benign

0.64

Sift4G

Benign

0.72

Polyphen

0.0010

Vest4

0.12

MVP

0.38

MPC

0.70

ClinPred

0.026

GERP RS

2.1

Varity_R

0.076

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over