chr6-24422315-G-C

Variant names:

• chr6-24422315-G-C
• rs7738943
• NM_020662.4:c.1108-622G>C

Variant summary

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

The NM_020662.4(MRS2):​c.1108-622G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 152,164 control chromosomes in the GnomAD database, including 611 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 0.084 (611 hom., cov: 32)
• Consequence: MRS2 NM_020662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020662.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	NM_020662.4	MANE Select	c.1108-622G>C		intron	N/A	NP_065713.1	Q9HD23-1
	MRS2	NM_001286264.2		c.1117-622G>C		intron	N/A	NP_001273193.1	Q9HD23-4
	MRS2	NM_001286265.2		c.1108-622G>C		intron	N/A	NP_001273194.1	Q9HD23-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	ENST00000378386.8	TSL:1 MANE Select	c.1108-622G>C		intron	N/A	ENSP00000367637.3	Q9HD23-1
	MRS2	ENST00000378353.5	TSL:1	c.1108-622G>C		intron	N/A	ENSP00000367604.1	Q9HD23-2
	MRS2	ENST00000873844.1		c.1132-622G>C		intron	N/A	ENSP00000543903.1

Frequencies

GnomAD3 genomes AF: 0.0836 AC: 12714 AN: 152046 Hom.: 607 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0161

Gnomad EAS AF: 0.00576

Gnomad SAS AF: 0.0244

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0757

Gnomad OTH AF: 0.0918

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

GnomAD4 genome AF: 0.0836 AC: 12726 AN: 152164 Hom.: 611 Cov.: 32 AF XY: 0.0801 AC XY: 5956 AN XY: 74392

African (AFR) AF: 0.132 AC: 5457 AN: 41460

American (AMR) AF: 0.0634 AC: 969 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 56 AN: 3472

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5192

South Asian (SAS) AF: 0.0243 AC: 117 AN: 4824

European-Finnish (FIN) AF: 0.0584 AC: 619 AN: 10592

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0757 AC: 5147 AN: 68014

Other (OTH) AF: 0.0908 AC: 192 AN: 2114

Alfa AF: 0.0835 Hom.: 62

Bravo AF: 0.0879

Asia WGS AF: 0.0360 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.66
PhyloP100		-0.098
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: rs7738943; hg19: chr6-24422543;