rs11557064

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_016098.4(MPC1):c.106C>A(p.Leu36Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,613,922 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 45 hom., cov: 33)

Exomes 𝑓: 0.025 ( 589 hom. )

Consequence

MPC1
NM_016098.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 9.23

Publications

12 publications found

Variant links:

Genes affected

MPC1 (HGNC:21606): (mitochondrial pyruvate carrier 1) The protein encoded by this gene is part of an MPC1/MPC2 heterodimer that is responsible for transporting pyruvate into mitochondria. The encoded protein is found in the inner mitochondrial membrane. Defects in this gene are a cause of mitochondrial pyruvate carrier deficiency. Several transcript variants, some protein coding and one non-protein coding, have been found for this gene. [provided by RefSeq, Aug 2012]

MPC1 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
mitochondrial pyruvate carrier deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

MPC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

PM1

In a chain Mitochondrial pyruvate carrier 1 (size 107) in uniprot entity MPC1_HUMAN there are 6 pathogenic changes around while only 2 benign (75%) in NM_016098.4

BP4

Computational evidence support a benign effect (MetaRNN=0.010059357).

BP6

Variant 6-166366861-G-T is Benign according to our data. Variant chr6-166366861-G-T is described in ClinVar as Benign. ClinVar VariationId is 138240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0198 (3009/152284) while in subpopulation AMR AF = 0.0372 (569/15292). AF 95% confidence interval is 0.0347. There are 45 homozygotes in GnomAd4. There are 1361 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 45 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPC1	NM_016098.4 link	c.106C>A	p.Leu36Ile	missense_variant	Exon 3 of 5	ENST00000360961.11	NP_057182.1	Q9Y5U8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPC1	ENST00000360961.11 link	c.106C>A	p.Leu36Ile	missense_variant	Exon 3 of 5	5	NM_016098.4	ENSP00000354223.6		Q9Y5U8

Frequencies

GnomAD3 genomes

AF:

0.0198

AC:

3010

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00611

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0373

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.00377

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0290

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0173

AC:

4356

AN:

251432

AF XY:

0.0175

show subpopulations

Gnomad AFR exome

AF:

0.00560

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00545

Gnomad NFE exome

AF:

0.0275

Gnomad OTH exome

AF:

0.0215

GnomAD4 exome

AF:

0.0246

AC:

36006

AN:

1461638

Hom.:

589

Cov.:

AF XY:

0.0241

AC XY:

17510

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00472

AC:

158

AN:

33478

American (AMR)

AF:

0.0182

AC:

813

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0172

AC:

450

AN:

26130

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00342

AC:

295

AN:

86252

European-Finnish (FIN)

AF:

0.00575

AC:

307

AN:

53414

Middle Eastern (MID)

AF:

0.0317

AC:

183

AN:

5768

European-Non Finnish (NFE)

AF:

0.0291

AC:

32403

AN:

1111784

Other (OTH)

AF:

0.0231

AC:

1396

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

1839

3677

5516

7354

9193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1210

2420

3630

4840

6050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0198

AC:

3009

AN:

152284

Hom.:

Cov.:

AF XY:

0.0183

AC XY:

1361

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.00609

AC:

253

AN:

41558

American (AMR)

AF:

0.0372

AC:

569

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0167

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00394

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00377

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0290

AC:

1971

AN:

68020

Other (OTH)

AF:

0.0222

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

151

302

453

604

755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0231

Hom.:

102

Bravo

AF:

0.0212

TwinsUK

AF:

0.0329

AC:

122

ALSPAC

AF:

0.0280

AC:

108

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0293

AC:

252

ExAC

AF:

0.0167

AC:

2030

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0289

EpiControl

AF:

0.0337

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 22, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Dec 09, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

L;.

PhyloP100

9.2

PROVEAN

Benign

-0.37

N;.

REVEL

Uncertain

0.33

Sift

Benign

0.75

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0060

B;.

Vest4

0.26

MPC

0.72

ClinPred

0.072

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.14

gMVP

0.74

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over