6-24402943-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020662.4(MRS2):​c.-104C>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 949,482 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: MRS2 NM_020662.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.238
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRS2	NM_020662.4	c.-104C>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	ENST00000378386.8	NP_065713.1
MRS2	NM_020662.4	c.-104C>A		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>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 11	1	NM_020662.4	ENSP00000367637.3
MRS2	ENST00000378386.8	c.-104C>A		5_prime_UTR_variant	Exon 1 of 11	1	NM_020662.4	ENSP00000367637.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000105 AC: 1 AN: 949482 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 478052

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21012

American (AMR) AF: 0.00 AC: 0 AN: 24148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16788

East Asian (EAS) AF: 0.00 AC: 0 AN: 34142

South Asian (SAS) AF: 0.00 AC: 0 AN: 58164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4316

European-Non Finnish (NFE) AF: 0.00000140 AC: 1 AN: 713940

Other (OTH) AF: 0.00 AC: 0 AN: 42060

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		-0.24
PromoterAI		-0.061	Neutral
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

Other links and lift over

dbSNP: rs2295650; hg19: chr6-24403171;