6-24412349-C-T

Position:

• chr6-24412349-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020662.4(MRS2):​c.542C>T​(p.Pro181Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MRS2 NM_020662.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.60

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37857193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRS2	NM_020662.4	c.542C>T	p.Pro181Leu	missense_variant	5/11	ENST00000378386.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRS2	ENST00000378386.8	c.542C>T	p.Pro181Leu	missense_variant	5/11	1	NM_020662.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444876 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

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

May 23, 2024

The c.542C>T (p.P181L) alteration is located in exon 5 (coding exon 5) of the MRS2 gene. This alteration results from a C to T substitution at nucleotide position 542, causing the proline (P) at amino acid position 181 to be replaced by a leucine (L). 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	0.19
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.38	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	D;.;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;.;D;D
Sift4G	Uncertain	0.015	D;D;D;D
Polyphen		0.83	.;.;P;P
Vest4		0.35
MutPred		0.56		.;.;Loss of disorder (P = 0.1244);Loss of disorder (P = 0.1244);
MVP		0.55
MPC		0.63
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.16
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr6-24412577;