rs7769012

Positions:

• chr6-24410136-A-C
• chr6-24410136-A-G
• chr6-24410136-A-T

Variant summary

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

The NM_020662.4(MRS2):​c.414+563A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,792 control chromosomes in the GnomAD database, including 11,448 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 0.38 (11448 hom., cov: 31)
• Consequence: MRS2 NM_020662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRS2	NM_020662.4	c.414+563A>C		intron_variant		ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.414+563A>C		intron_variant		1	NM_020662.4	ENSP00000367637	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57678 AN: 151674 Hom.: 11406 Cov.: 31

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.379

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.381 AC: 57782 AN: 151792 Hom.: 11448 Cov.: 31 AF XY: 0.388 AC XY: 28781 AN XY: 74174

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.386

Alfa AF: 0.192 Hom.: 362

Bravo AF: 0.383

Asia WGS AF: 0.627 AC: 2179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.58
DANN	Benign	0.34

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: rs7769012; hg19: chr6-24410364;