rs1298764

chr6-24412082-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_020662.4(MRS2):c.415-140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 463,838 control chromosomes in the GnomAD database, including 438 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 0.035 (107 hom., cov: 31)
  • Exomes 𝑓: 0.044 (331 hom.)
• Consequence: MRS2 NM_020662.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0353 (5321/150578) while in subpopulation NFE AF= 0.0468 (3167/67726). AF 95% confidence interval is 0.0454. There are 107 homozygotes in gnomad4. There are 2659 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 107 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.415-140C>T		intron_variant		ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378386.8	c.415-140C>T		intron_variant		1	NM_020662.4	P1

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5324 AN: 150486 Hom.: 107 Cov.: 31

Gnomad AFR AF: 0.00858

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0410

Gnomad ASJ AF: 0.0660

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0620

Gnomad MID AF: 0.0548

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0412

GnomAD4 exome AF: 0.0435 AC: 13633 AN: 313260 Hom.: 331 AF XY: 0.0440 AC XY: 6941 AN XY: 157646

Gnomad4 AFR exome AF: 0.00791

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0671

Gnomad4 EAS exome AF: 0.00399

Gnomad4 SAS exome AF: 0.0295

Gnomad4 FIN exome AF: 0.0628

Gnomad4 NFE exome AF: 0.0461

Gnomad4 OTH exome AF: 0.0456

GnomAD4 genome AF: 0.0353 AC: 5321 AN: 150578 Hom.: 107 Cov.: 31 AF XY: 0.0362 AC XY: 2659 AN XY: 73466

Gnomad4 AFR AF: 0.00855

Gnomad4 AMR AF: 0.0410

Gnomad4 ASJ AF: 0.0660

Gnomad4 EAS AF: 0.0144

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0620

Gnomad4 NFE AF: 0.0468

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0389 Hom.: 12

Bravo AF: 0.0326

Asia WGS AF: 0.0200 AC: 70 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.47
Dann	Benign	0.36

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: rs1298764; hg19: chr6-24412310;