Variant 6-13801341-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001031713.4(MCUR1):c.688G>A(p.Asp230Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MCUR1
NM_001031713.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.97

Variant links:

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]

MCUR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
MCUR1	NM_001031713.4 linkuse as main transcript	c.688G>A	p.Asp230Asn	missense_variant	4/9	ENST00000379170.9	NP_001026883.1
MCUR1	XM_047419249.1 linkuse as main transcript	c.931G>A	p.Asp311Asn	missense_variant	4/9		XP_047275205.1
MCUR1	XM_011514802.2 linkuse as main transcript	c.688G>A	p.Asp230Asn	missense_variant	4/9		XP_011513104.1
MCUR1	XR_007059329.1 linkuse as main transcript	n.816G>A		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUR1	ENST00000379170.9 linkuse as main transcript	c.688G>A	p.Asp230Asn	missense_variant	4/9	1	NM_001031713.4	ENSP00000368468	P1	Q96AQ8-1
MCUR1	ENST00000607303.1 linkuse as main transcript	c.7G>A	p.Asp3Asn	missense_variant	1/7	3		ENSP00000476106
MCUR1	ENST00000488770.1 linkuse as main transcript	c.*500G>A		3_prime_UTR_variant, NMD_transcript_variant	5/10	2		ENSP00000476162		Q96AQ8-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

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

GnomAD3 exomes

AF:

0.0000758

AC:

AN:

250692

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135556

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000979

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460828

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000824

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.688G>A (p.D230N) alteration is located in exon 4 (coding exon 4) of the MCUR1 gene. This alteration results from a G to A substitution at nucleotide position 688, causing the aspartic acid (D) at amino acid position 230 to be replaced by an asparagine (N). 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

Pathogenic

0.66

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.86

M_CAP

Benign

0.053

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.35

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.89

MutPred

0.65

Gain of MoRF binding (P = 0.0304);

MVP

0.70

MPC

0.52

ClinPred

0.68

GERP RS

5.3

Varity_R

0.67

gMVP

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over