6-13801319-C-G

Position:

• chr6-13801319-C-G

Variant summary

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

The ENST00000379170.9(MCUR1):​c.710G>C​(p.Ser237Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MCUR1 ENST00000379170.9 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97

Genes affected

MCUR1 (HGNC:21097): (mitochondrial calcium uniporter regulator 1) Involved in calcium import into the mitochondrion and positive regulation of mitochondrial calcium ion concentration. Is integral component of mitochondrial inner membrane. [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
MCUR1	NM_001031713.4	c.710G>C	p.Ser237Thr	missense_variant	4/9	ENST00000379170.9	NP_001026883.1
MCUR1	XM_047419249.1	c.953G>C	p.Ser318Thr	missense_variant	4/9		XP_047275205.1
MCUR1	XM_011514802.2	c.710G>C	p.Ser237Thr	missense_variant	4/9		XP_011513104.1
MCUR1	XR_007059329.1	n.838G>C		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUR1	ENST00000379170.9	c.710G>C	p.Ser237Thr	missense_variant	4/9	1	NM_001031713.4	ENSP00000368468	P1
MCUR1	ENST00000607303.1	c.29G>C	p.Ser10Thr	missense_variant	1/7	3		ENSP00000476106
MCUR1	ENST00000488770.1	c.*522G>C		3_prime_UTR_variant, NMD_transcript_variant	5/10	2		ENSP00000476162

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460864 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726772

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: 8.99e-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

Mar 02, 2023

The c.710G>C (p.S237T) alteration is located in exon 4 (coding exon 4) of the MCUR1 gene. This alteration results from a G to C substitution at nucleotide position 710, causing the serine (S) at amino acid position 237 to be replaced by a threonine (T). 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	0.33
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.36
Sift	Benign	0.27	T
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.53		Loss of phosphorylation at S237 (P = 0.0519);
MVP		0.68
MPC		0.50
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.45
gMVP		0.46

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: chr6-13801551;