6-24415073-T-G

Position:

• chr6-24415073-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020662.4(MRS2):​c.629T>G​(p.Leu210Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MRS2 NM_020662.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.70

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08879018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.629T>G	p.Leu210Arg	missense_variant	6/11	ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378386.8	c.629T>G	p.Leu210Arg	missense_variant	6/11	1	NM_020662.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74384

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.629T>G (p.L210R) alteration is located in exon 6 (coding exon 6) of the MRS2 gene. This alteration results from a T to G substitution at nucleotide position 629, causing the leucine (L) at amino acid position 210 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.061	.;T;.;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.72	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.089	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.090	.;.;N;N
MutationTaster	Benign	1.0	D;D;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.010	N;.;N;N
REVEL	Benign	0.096
Sift	Benign	0.57	T;.;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.0010	.;.;B;B
Vest4		0.27
MutPred		0.54		.;.;Loss of stability (P = 0.0591);Loss of stability (P = 0.0591);
MVP		0.36
MPC		0.52
ClinPred		0.30	T
GERP RS		4.8
Varity_R		0.14
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1253928230; hg19: chr6-24415301;