chr6-24407305-A-G

Variant names:

• chr6-24407305-A-G
• rs1277347
• NM_020662.4:c.265-1103A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286264.2(MRS2):​c.265-1103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.988 in 152,306 control chromosomes in the GnomAD database, including 74,399 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 0.99 (74399 hom., cov: 33)
• Consequence: MRS2 NM_001286264.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286264.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	NM_020662.4	MANE Select	c.265-1103A>G		intron	N/A	NP_065713.1
	MRS2	NM_001286264.2		c.265-1103A>G		intron	N/A	NP_001273193.1
	MRS2	NM_001286265.2		c.265-1103A>G		intron	N/A	NP_001273194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	ENST00000378386.8	TSL:1 MANE Select	c.265-1103A>G		intron	N/A	ENSP00000367637.3
	MRS2	ENST00000378353.5	TSL:1	c.265-1103A>G		intron	N/A	ENSP00000367604.1
	MRS2	ENST00000873844.1		c.289-1103A>G		intron	N/A	ENSP00000543903.1

Frequencies

GnomAD3 genomes AF: 0.988 AC: 150395 AN: 152188 Hom.: 74342 Cov.: 33

Gnomad AFR AF: 0.961

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.991

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.988

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

GnomAD4 genome AF: 0.988 AC: 150511 AN: 152306 Hom.: 74399 Cov.: 33 AF XY: 0.988 AC XY: 73589 AN XY: 74464

African (AFR) AF: 0.961 AC: 39936 AN: 41556

American (AMR) AF: 0.992 AC: 15171 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3467 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5188 AN: 5188

South Asian (SAS) AF: 1.00 AC: 4824 AN: 4824

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68024 AN: 68042

Other (OTH) AF: 0.988 AC: 2088 AN: 2114

Alfa AF: 0.995 Hom.: 3872

Bravo AF: 0.987

Asia WGS AF: 0.999 AC: 3466 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.94
DANN	Benign	0.70
PhyloP100		-0.15
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: rs1277347; hg19: chr6-24407533;