chr6-24405129-A-G

Variant names:

• chr6-24405129-A-G
• rs2273606
• NM_020662.4:c.191-39A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MRS2	NM_020662.4	c.191-39A>G		intron_variant	Intron 1 of 10	ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.191-39A>G		intron_variant	Intron 1 of 10	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

GnomAD2 exomes AF: 0.143 AC: 35795 AN: 250448 AF XY: 0.147

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 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

African (AFR) AF: 0.0206 AC: 638 AN: 30904

American (AMR) AF: 0.0751 AC: 3342 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 3263 AN: 25344

East Asian (EAS) AF: 0.149 AC: 5824 AN: 39078

South Asian (SAS) AF: 0.151 AC: 12606 AN: 83586

European-Finnish (FIN) AF: 0.262 AC: 13966 AN: 53208

Middle Eastern (MID) AF: 0.168 AC: 925 AN: 5498

European-Non Finnish (NFE) AF: 0.147 AC: 146548 AN: 995368

Other (OTH) AF: 0.141 AC: 7891 AN: 56142

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

African (AFR) AF: 0.0256 AC: 1065 AN: 41552

American (AMR) AF: 0.0989 AC: 1513 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3468

East Asian (EAS) AF: 0.158 AC: 817 AN: 5182

South Asian (SAS) AF: 0.145 AC: 700 AN: 4820

European-Finnish (FIN) AF: 0.269 AC: 2846 AN: 10572

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10503 AN: 67986

Other (OTH) AF: 0.128 AC: 271 AN: 2114

Alfa AF: 0.144 Hom.: 1246

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
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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