chr15-41696827-C-T

Variant names:

• chr15-41696827-C-T
• rs140642216
• NM_001400225.1:c.1817C>T

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.1817C>T​(p.Ala606Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,599,752 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (9 hom.)
• Consequence: MGA NM_001400225.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0130
• Publications: 6 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=0.0024363399).
• BP6: Variant 15-41696827-C-T is Benign according to our data. Variant chr15-41696827-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 778487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 5 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.1817C>T	p.Ala606Val	missense	Exon 3 of 24	NP_001387154.1	A0A994J6L2
	MGA	NM_001164273.2		c.1817C>T	p.Ala606Val	missense	Exon 3 of 24	NP_001157745.1	Q8IWI9-4
	MGA	NM_001080541.3		c.1817C>T	p.Ala606Val	missense	Exon 3 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.1817C>T	p.Ala606Val	missense	Exon 3 of 24	ENSP00000515495.1	A0A994J6L2
	MGA	ENST00000566586.6	TSL:1	c.1817C>T	p.Ala606Val	missense	Exon 3 of 23	ENSP00000456141.1	Q8IWI9-3
	MGA	ENST00000916432.1		c.1817C>T	p.Ala606Val	missense	Exon 3 of 24	ENSP00000586491.1

Frequencies

GnomAD3 genomes AF: 0.00278 AC: 423 AN: 152124 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00344

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00252 AC: 564 AN: 223542 AF XY: 0.00228

Gnomad AFR exome AF: 0.000223

Gnomad AMR exome AF: 0.00271

Gnomad ASJ exome AF: 0.0111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.00336

Gnomad OTH exome AF: 0.00320

GnomAD4 exome AF: 0.00310 AC: 4482 AN: 1447510 Hom.: 9 Cov.: 32 AF XY: 0.00296 AC XY: 2126 AN XY: 718568

African (AFR) AF: 0.000451 AC: 15 AN: 33254

American (AMR) AF: 0.00270 AC: 113 AN: 41920

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 269 AN: 25758

East Asian (EAS) AF: 0.00 AC: 0 AN: 39306

South Asian (SAS) AF: 0.0000238 AC: 2 AN: 83910

European-Finnish (FIN) AF: 0.000626 AC: 33 AN: 52744

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5760

European-Non Finnish (NFE) AF: 0.00350 AC: 3864 AN: 1104878

Other (OTH) AF: 0.00295 AC: 177 AN: 59980

GnomAD4 genome AF: 0.00278 AC: 423 AN: 152242 Hom.: 5 Cov.: 32 AF XY: 0.00275 AC XY: 205 AN XY: 74430

African (AFR) AF: 0.000795 AC: 33 AN: 41534

American (AMR) AF: 0.00634 AC: 97 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00344 AC: 234 AN: 68014

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00346 Hom.: 4

Bravo AF: 0.00308

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000266 AC: 1

ESP6500EA AF: 0.00364 AC: 30

ExAC AF: 0.00225 AC: 271

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.94
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.013
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.053
Sift	Benign	0.39	T
Sift4G	Benign	0.94	T
Vest4		0.12
MVP		0.093
MPC		0.094
ClinPred		0.0054	T
GERP RS		-0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.14
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs140642216; hg19: chr15-41989025; COSMIC: COSV99062571; COSMIC: COSV99062571;