rs1298764

Variant names:

• chr6-24412082-C-T
• rs1298764
• NM_020662.4:c.415-140C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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).
• 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 107 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRS2	NM_020662.4	c.415-140C>T		intron_variant	Intron 4 of 10	ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.415-140C>T		intron_variant	Intron 4 of 10	1	NM_020662.4	ENSP00000367637.3

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

African (AFR) AF: 0.00791 AC: 64 AN: 8088

American (AMR) AF: 0.0333 AC: 235 AN: 7054

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 613 AN: 9136

East Asian (EAS) AF: 0.00399 AC: 84 AN: 21054

South Asian (SAS) AF: 0.0295 AC: 145 AN: 4916

European-Finnish (FIN) AF: 0.0628 AC: 1396 AN: 22218

Middle Eastern (MID) AF: 0.0432 AC: 59 AN: 1366

European-Non Finnish (NFE) AF: 0.0461 AC: 10228 AN: 221674

Other (OTH) AF: 0.0456 AC: 809 AN: 17754

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

African (AFR) AF: 0.00855 AC: 352 AN: 41154

American (AMR) AF: 0.0410 AC: 620 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 229 AN: 3468

East Asian (EAS) AF: 0.0144 AC: 74 AN: 5150

South Asian (SAS) AF: 0.0340 AC: 163 AN: 4798

European-Finnish (FIN) AF: 0.0620 AC: 612 AN: 9878

Middle Eastern (MID) AF: 0.0563 AC: 16 AN: 284

European-Non Finnish (NFE) AF: 0.0468 AC: 3167 AN: 67726

Other (OTH) AF: 0.0408 AC: 85 AN: 2082

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs1298764; hg19: chr6-24412310;