rs2273606

Positions:

• chr6-24405129-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020662.4(MRS2):​c.191-39A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,485,850 control chromosomes in the GnomAD database, including 16,900 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 0.12 (1464 hom., cov: 32)
  • Exomes 𝑓: 0.15 (15436 hom.)
• Consequence: MRS2 NM_020662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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]

MRS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRS2	NM_020662.4	c.191-39A>G		intron_variant		ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.191-39A>G		intron_variant		1	NM_020662.4	ENSP00000367637.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18315 AN: 152074 Hom.: 1464 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.0990

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.143 AC: 35795 AN: 250448 Hom.: 3072 AF XY: 0.147 AC XY: 19959 AN XY: 135364

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.0712

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.153

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.143

GnomAD4 exome AF: 0.146 AC: 195003 AN: 1333658 Hom.: 15436 Cov.: 19 AF XY: 0.147 AC XY: 98505 AN XY: 670942

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.0751

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.120 AC: 18307 AN: 152192 Hom.: 1464 Cov.: 32 AF XY: 0.126 AC XY: 9354 AN XY: 74400

Gnomad4 AFR AF: 0.0256

Gnomad4 AMR AF: 0.0989

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.128

Alfa AF: 0.140 Hom.: 867

Bravo AF: 0.102

Asia WGS AF: 0.151 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.98
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs2273606; hg19: chr6-24405357; COSMIC: COSV51234137;