8-71844142-C-G

Position:

• chr8-71844142-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005098.4(MSC):​c.37G>C​(p.Glu13Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MSC NM_005098.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

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

ACMG classification

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=0.26353598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSC	NM_005098.4	c.37G>C	p.Glu13Gln	missense_variant	1/2	ENST00000325509.5	NP_005089.2
MSC-AS1	NR_033652.1	n.583-87C>G		intron_variant, non_coding_transcript_variant
MSC-AS1	NR_033651.1	n.27C>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSC	ENST00000325509.5	c.37G>C	p.Glu13Gln	missense_variant	1/2	1	NM_005098.4	ENSP00000321445	P1
MSC-AS1	ENST00000518916.5			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 03, 2022

The c.37G>C (p.E13Q) alteration is located in exon 1 (coding exon 1) of the MSC gene. This alteration results from a G to C substitution at nucleotide position 37, causing the glutamic acid (E) at amino acid position 13 to be replaced by a glutamine (Q). 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	0.15
BayesDel_addAF	Uncertain	0.084	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.021
Eigen_PC	Benign	0.029
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.73	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.60	D
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	0.90	D
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.35	N
REVEL	Uncertain	0.29
Sift	Benign	0.071	T
Sift4G	Benign	0.45	T
Polyphen		0.85	P
Vest4		0.23
MutPred		0.14		Gain of MoRF binding (P = 0.0867);
MVP		0.63
MPC		1.0
ClinPred		0.56	D
GERP RS		3.2
Varity_R		0.18
gMVP		0.30

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.

Other links and lift over

hg19: chr8-72756377; COSMIC: COSV100335776; COSMIC: COSV100335776;