6-13801374-G-C

Position:

• chr6-13801374-G-C

Variant summary

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

The NM_001031713.4(MCUR1):​c.655C>G​(p.Gln219Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: MCUR1 NM_001031713.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.43

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40794966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCUR1	NM_001031713.4	c.655C>G	p.Gln219Glu	missense_variant	4/9	ENST00000379170.9	NP_001026883.1
MCUR1	XM_047419249.1	c.898C>G	p.Gln300Glu	missense_variant	4/9		XP_047275205.1
MCUR1	XM_011514802.2	c.655C>G	p.Gln219Glu	missense_variant	4/9		XP_011513104.1
MCUR1	XR_007059329.1	n.783C>G		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUR1	ENST00000379170.9	c.655C>G	p.Gln219Glu	missense_variant	4/9	1	NM_001031713.4	ENSP00000368468	P1
MCUR1	ENST00000488770.1	c.*467C>G		3_prime_UTR_variant, NMD_transcript_variant	5/10	2		ENSP00000476162
MCUR1	ENST00000607303.1			upstream_gene_variant		3		ENSP00000476106

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

Nov 30, 2021

The c.655C>G (p.Q219E) alteration is located in exon 4 (coding exon 4) of the MCUR1 gene. This alteration results from a C to G substitution at nucleotide position 655, causing the glutamine (Q) at amino acid position 219 to be replaced by a glutamic acid (E). 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	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.98	D
Vest4		0.25
MutPred		0.73		Loss of MoRF binding (P = 0.0659);
MVP		0.62
MPC		0.24
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.41
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr6-13801606;