rs3761788

chr6-24415152-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020662.4(MRS2):c.708G>A(p.Gln236=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,588,986 control chromosomes in the GnomAD database, including 3,928 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (219 hom., cov: 32)
  • Exomes 𝑓: 0.066 (3709 hom.)
• Consequence: MRS2 NM_020662.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388

Genes affected

MRS2 (HGNC:13785): (magnesium transporter MRS2) Enables magnesium ion transmembrane transporter activity. Involved in mitochondrial magnesium ion transmembrane transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP7: Synonymous conserved (PhyloP=0.388 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.708G>A	p.Gln236=	synonymous_variant	6/11	ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378386.8	c.708G>A	p.Gln236=	synonymous_variant	6/11	1	NM_020662.4	P1

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6968 AN: 152166 Hom.: 219 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0382

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.0522

GnomAD3 exomes AF: 0.0459 AC: 11447 AN: 249324 Hom.: 406 AF XY: 0.0451 AC XY: 6078 AN XY: 134710

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.0294

Gnomad ASJ exome AF: 0.00847

Gnomad EAS exome AF: 0.00273

Gnomad SAS exome AF: 0.00920

Gnomad FIN exome AF: 0.0575

Gnomad NFE exome AF: 0.0735

Gnomad OTH exome AF: 0.0446

GnomAD4 exome AF: 0.0655 AC: 94137 AN: 1436704 Hom.: 3709 Cov.: 30 AF XY: 0.0638 AC XY: 45335 AN XY: 710952

Gnomad4 AFR exome AF: 0.00930

Gnomad4 AMR exome AF: 0.0306

Gnomad4 ASJ exome AF: 0.00934

Gnomad4 EAS exome AF: 0.00265

Gnomad4 SAS exome AF: 0.00930

Gnomad4 FIN exome AF: 0.0600

Gnomad4 NFE exome AF: 0.0777

Gnomad4 OTH exome AF: 0.0536

GnomAD4 genome AF: 0.0457 AC: 6966 AN: 152282 Hom.: 219 Cov.: 32 AF XY: 0.0435 AC XY: 3239 AN XY: 74464

Gnomad4 AFR AF: 0.0135

Gnomad4 AMR AF: 0.0381

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.00726

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0719

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0625 Hom.: 544

Bravo AF: 0.0435

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	1.3
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs3761788; hg19: chr6-24415380; COSMIC: COSV51234145;