rs2295650

Positions:

• chr6-24402943-C-G

Variant summary

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

The NM_020662.4(MRS2):​c.-104C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00744 in 1,101,776 control chromosomes in the GnomAD database, including 341 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 0.0096 (45 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (296 hom.)
• Consequence: MRS2 NM_020662.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.-104C>G		5_prime_UTR_variant	1/11	ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378386.8	c.-104C>G		5_prime_UTR_variant	1/11	1	NM_020662.4	P1

Frequencies

GnomAD3 genomes AF: 0.00957 AC: 1456 AN: 152214 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.00621

GnomAD4 exome AF: 0.00710 AC: 6743 AN: 949444 Hom.: 296 Cov.: 12 AF XY: 0.00646 AC XY: 3090 AN XY: 478034

Gnomad4 AFR exome AF: 0.000714

Gnomad4 AMR exome AF: 0.0771

Gnomad4 ASJ exome AF: 0.000179

Gnomad4 EAS exome AF: 0.0989

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.0265

Gnomad4 NFE exome AF: 0.000332

Gnomad4 OTH exome AF: 0.00628

GnomAD4 genome AF: 0.00958 AC: 1459 AN: 152332 Hom.: 45 Cov.: 33 AF XY: 0.0117 AC XY: 869 AN XY: 74490

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00603 Hom.: 2

Bravo AF: 0.0112

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2295650; hg19: chr6-24403171; COSMIC: COSV51235710; COSMIC: COSV51235710;