15-41729239-G-C

Position:

• chr15-41729239-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The ENST00000703841.1(MGA):​c.3733G>C​(p.Glu1245Gln) variant causes a missense change. 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 Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MGA ENST00000703841.1 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.39

Genes affected

MGA (HGNC:14010): (MAX dimerization protein MGA) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell fate specification and positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Part of MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-41729239-G-C is Pathogenic according to our data. Variant chr15-41729239-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 800331.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.38238603). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGA	NM_001400225.1	c.3733G>C	p.Glu1245Gln	missense_variant	11/24	ENST00000703841.1	NP_001387154.1
MGA	XM_017022029.3	c.2362G>C	p.Glu788Gln	missense_variant	10/23		XP_016877518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGA	ENST00000703841.1	c.3733G>C	p.Glu1245Gln	missense_variant	11/24		NM_001400225.1	ENSP00000515495	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Multiple myeloma Pathogenic:1

Likely pathogenic, no assertion criteria provided

clinical testing

Xiao lab, Department of Pathology, Memorial Sloan Kettering Cancer Center

Aug 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
DANN	Uncertain	1.0
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D;.;.
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Uncertain	0.11	D
MutationAssessor	Uncertain	2.1	M;M;M;M
MutationTaster	Benign	0.92	N;N;N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Benign	0.068	T;D;T;D
Vest4		0.49
MutPred		0.24		Gain of MoRF binding (P = 0.04);Gain of MoRF binding (P = 0.04);Gain of MoRF binding (P = 0.04);Gain of MoRF binding (P = 0.04);
MVP		0.54
MPC		0.29
ClinPred		0.79	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1595889508; hg19: chr15-42021437;