Variant 6-13814296-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000379170.9(MCUR1):c.134T>C(p.Leu45Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000133 in 1,499,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L45V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

MCUR1
ENST00000379170.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.691

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:

LOC107986571 (HGNC:):

LOC107986571 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20882508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCUR1	NM_001031713.4 linkuse as main transcript	c.134T>C	p.Leu45Pro	missense_variant	1/9	ENST00000379170.9	NP_001026883.1
LOC107986571	XR_001743986.3 linkuse as main transcript	n.280+207A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCUR1	ENST00000379170.9 linkuse as main transcript	c.134T>C	p.Leu45Pro	missense_variant	1/9	1	NM_001031713.4	ENSP00000368468	P1	Q96AQ8-1
MCUR1	ENST00000488770.1 linkuse as main transcript	c.134T>C	p.Leu45Pro	missense_variant, NMD_transcript_variant	1/10	2		ENSP00000476162		Q96AQ8-2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151668

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:

0.000195

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

GnomAD4 exome

AF:

7.42e-7

AC:

AN:

1347348

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

664284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000325

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Jan 03, 2024

The c.134T>C (p.L45P) alteration is located in exon 1 (coding exon 1) of the MCUR1 gene. This alteration results from a T to C substitution at nucleotide position 134, causing the leucine (L) at amino acid position 45 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

0.063

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.42

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.2

REVEL

Benign

0.14

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.98

Vest4

0.20

MutPred

0.34

Loss of stability (P = 0.0019);

MVP

0.47

MPC

0.21

ClinPred

0.38

GERP RS

2.3

Varity_R

0.27

gMVP

0.45

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