6-24402943-C-G

Variant names:

• chr6-24402943-C-G
• rs2295650
• NM_020662.4:c.-104C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.76).
• 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 rank	MANE	Protein	UniProt
MRS2	NM_020662.4	c.-104C>G		5_prime_UTR_variant	Exon 1 of 11	ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.-104C>G		5_prime_UTR_variant	Exon 1 of 11	1	NM_020662.4	ENSP00000367637.3

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

African (AFR) AF: 0.000714 AC: 15 AN: 21012

American (AMR) AF: 0.0771 AC: 1860 AN: 24128

Ashkenazi Jewish (ASJ) AF: 0.000179 AC: 3 AN: 16788

East Asian (EAS) AF: 0.0989 AC: 3376 AN: 34126

South Asian (SAS) AF: 0.00103 AC: 60 AN: 58164

European-Finnish (FIN) AF: 0.0265 AC: 925 AN: 34910

Middle Eastern (MID) AF: 0.000695 AC: 3 AN: 4316

European-Non Finnish (NFE) AF: 0.000332 AC: 237 AN: 713944

Other (OTH) AF: 0.00628 AC: 264 AN: 42056

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

African (AFR) AF: 0.00137 AC: 57 AN: 41582

American (AMR) AF: 0.0359 AC: 549 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.0780 AC: 403 AN: 5166

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4828

European-Finnish (FIN) AF: 0.0333 AC: 354 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00100 AC: 68 AN: 68026

Other (OTH) AF: 0.00614 AC: 13 AN: 2116

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
PhyloP100		-0.24
PromoterAI		-0.10	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=298/2	polymorphism

Splicing

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

Other links and lift over

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