chr6-24423396-C-T

Variant names:

• chr6-24423396-C-T
• rs13735
• ENST00000378353.5:c.*340C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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 = 0.74 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378353.5. 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.1222-188C>T		intron	N/A	NP_065713.1
	MRS2	NM_001286265.2		c.*340C>T		3_prime_UTR	Exon 10 of 10	NP_001273194.1
	MRS2	NM_001286264.2		c.1231-188C>T		intron	N/A	NP_001273193.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	ENST00000378353.5	TSL:1	c.*340C>T		3_prime_UTR	Exon 10 of 10	ENSP00000367604.1
	MRS2	ENST00000378386.8	TSL:1 MANE Select	c.1222-188C>T		intron	N/A	ENSP00000367637.3
	MRS2	ENST00000443868.6	TSL:2	c.1231-188C>T		intron	N/A	ENSP00000399585.2

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

African (AFR) AF: 0.451 AC: 4813 AN: 10680

American (AMR) AF: 0.484 AC: 6708 AN: 13868

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 2747 AN: 10926

East Asian (EAS) AF: 0.764 AC: 19930 AN: 26072

South Asian (SAS) AF: 0.471 AC: 12081 AN: 25634

European-Finnish (FIN) AF: 0.459 AC: 11227 AN: 24466

Middle Eastern (MID) AF: 0.361 AC: 561 AN: 1552

European-Non Finnish (NFE) AF: 0.357 AC: 74069 AN: 207760

Other (OTH) AF: 0.408 AC: 8357 AN: 20494

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

African (AFR) AF: 0.450 AC: 18647 AN: 41414

American (AMR) AF: 0.448 AC: 6836 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 924 AN: 3468

East Asian (EAS) AF: 0.759 AC: 3922 AN: 5164

South Asian (SAS) AF: 0.485 AC: 2334 AN: 4816

European-Finnish (FIN) AF: 0.466 AC: 4912 AN: 10530

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24536 AN: 67924

Other (OTH) AF: 0.424 AC: 893 AN: 2108

Alfa AF: 0.387 Hom.: 1768

Bravo AF: 0.420

Asia WGS AF: 0.628 AC: 2184 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	0.068
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=99/1	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: rs13735; hg19: chr6-24423624;