rs13735

Positions:

• chr6-24423396-C-T

Variant summary

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

The ENST00000378353.5(MRS2):​c.*340C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 493,340 control chromosomes in the GnomAD database, including 45,264 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 0.42 (13705 hom., cov: 32)
  • Exomes 𝑓: 0.41 (31559 hom.)
• Consequence: MRS2 ENST00000378353.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.1222-188C>T		intron_variant		ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378353.5	c.*340C>T		3_prime_UTR_variant	10/10	1
MRS2	ENST00000378386.8	c.1222-188C>T		intron_variant		1	NM_020662.4	P1
MRS2	ENST00000274747.11	c.1072-188C>T		intron_variant		2
MRS2	ENST00000443868.6	c.1231-188C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63420 AN: 151770 Hom.: 13665 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.411 AC: 140493 AN: 341452 Hom.: 31559 Cov.: 4 AF XY: 0.411 AC XY: 73185 AN XY: 178078

Gnomad4 AFR exome AF: 0.451

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.764

Gnomad4 SAS exome AF: 0.471

Gnomad4 FIN exome AF: 0.459

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.418 AC: 63523 AN: 151888 Hom.: 13705 Cov.: 32 AF XY: 0.424 AC XY: 31461 AN XY: 74206

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.424

Alfa AF: 0.385 Hom.: 1690

Bravo AF: 0.420

Asia WGS AF: 0.628 AC: 2184 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	0.068
DANN	Benign	0.55

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: rs13735; hg19: chr6-24423624;