chr15-41669882-C-G

Variant names:

• chr15-41669882-C-G
• rs182187974
• NM_001400225.1:c.988C>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001400225.1(MGA):​c.988C>G​(p.Arg330Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00716 in 1,613,900 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0074 (63 hom.)
• Consequence: MGA NM_001400225.1 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.661
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0068923235).
• BP6: Variant 15-41669882-C-G is Benign according to our data. Variant chr15-41669882-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 789331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400225.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGA	NM_001400225.1	MANE Select	c.988C>G	p.Arg330Gly	missense	Exon 2 of 24	NP_001387154.1	A0A994J6L2
	MGA	NM_001164273.2		c.988C>G	p.Arg330Gly	missense	Exon 2 of 24	NP_001157745.1	Q8IWI9-4
	MGA	NM_001080541.3		c.988C>G	p.Arg330Gly	missense	Exon 2 of 23	NP_001074010.2	Q8IWI9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGA	ENST00000703841.1	MANE Select	c.988C>G	p.Arg330Gly	missense	Exon 2 of 24	ENSP00000515495.1	A0A994J6L2
	MGA	ENST00000566586.6	TSL:1	c.988C>G	p.Arg330Gly	missense	Exon 2 of 23	ENSP00000456141.1	Q8IWI9-3
	MGA	ENST00000916432.1		c.988C>G	p.Arg330Gly	missense	Exon 2 of 24	ENSP00000586491.1

Frequencies

GnomAD3 genomes AF: 0.00464 AC: 706 AN: 152122 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000755

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00837

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00403 AC: 998 AN: 247396 AF XY: 0.00395

Gnomad AFR exome AF: 0.00142

Gnomad AMR exome AF: 0.00272

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000835

Gnomad NFE exome AF: 0.00717

Gnomad OTH exome AF: 0.00497

GnomAD4 exome AF: 0.00743 AC: 10857 AN: 1461660 Hom.: 63 Cov.: 31 AF XY: 0.00714 AC XY: 5189 AN XY: 727114

African (AFR) AF: 0.00116 AC: 39 AN: 33480

American (AMR) AF: 0.00284 AC: 127 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00137 AC: 118 AN: 86258

European-Finnish (FIN) AF: 0.00133 AC: 71 AN: 53402

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00910 AC: 10115 AN: 1111822

Other (OTH) AF: 0.00628 AC: 379 AN: 60374

GnomAD4 genome AF: 0.00464 AC: 706 AN: 152240 Hom.: 4 Cov.: 32 AF XY: 0.00394 AC XY: 293 AN XY: 74450

African (AFR) AF: 0.00166 AC: 69 AN: 41530

American (AMR) AF: 0.00314 AC: 48 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.000755 AC: 8 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00837 AC: 569 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00704 Hom.: 5

Bravo AF: 0.00471

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00215 AC: 8

ESP6500EA AF: 0.00770 AC: 63

ExAC AF: 0.00387 AC: 467

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00676

EpiControl AF: 0.00694

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.063
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.66
PrimateAI	Benign	0.21	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.046	D
Vest4		0.27
MVP		0.23
MPC		0.12
ClinPred		0.035	T
GERP RS		4.7
gMVP		0.22
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs182187974; hg19: chr15-41962080;