rs7738943

chr6-24422315-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.1108-622G>C		intron_variant		ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378386.8	c.1108-622G>C		intron_variant		1	NM_020662.4	P1
MRS2	ENST00000378353.5	c.1108-622G>C		intron_variant		1
MRS2	ENST00000274747.11	c.958-622G>C		intron_variant		2
MRS2	ENST00000443868.6	c.1117-622G>C		intron_variant		2

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

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0634

Gnomad4 ASJ AF: 0.0161

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.0243

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.0757

Gnomad4 OTH AF: 0.0908

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.8
Dann	Benign	0.66

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: rs7738943; hg19: chr6-24422543;