6-24405180-G-C

Position:

• chr6-24405180-G-C

Variant summary

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

The NM_020662.4(MRS2):​c.203G>C​(p.Arg68Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRS2 NM_020662.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRS2	NM_020662.4	c.203G>C	p.Arg68Pro	missense_variant	2/11	ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.203G>C	p.Arg68Pro	missense_variant	2/11	1	NM_020662.4	ENSP00000367637	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Dec 06, 2022

The c.203G>C (p.R68P) alteration is located in exon 2 (coding exon 2) of the MRS2 gene. This alteration results from a G to C substitution at nucleotide position 203, causing the arginine (R) at amino acid position 68 to be replaced by a proline (P). 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	0.14
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T;.;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.57	D;D;D;D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M;.;M;M
MutationTaster	Benign	1.0	D;N;N;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.2	N;D;N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Uncertain	0.046	D;T;T;T
Polyphen		0.96, 0.99	.;.;D;D
Vest4		0.72
MutPred		0.40		Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);Loss of MoRF binding (P = 0.0255);
MVP		0.71
MPC		1.3
ClinPred		0.90	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-24405408;