Variant 6-166365976-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016098.4(MPC1):c.303C>T(p.His101=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 1,611,590 control chromosomes in the GnomAD database, including 2,662 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 165 hom., cov: 33)

Exomes 𝑓: 0.055 ( 2497 hom. )

Consequence

MPC1
NM_016098.4 splice_region, synonymous

Scores

Splicing: ADA: 0.001384

Clinical Significance

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

Conservation

PhyloP100: 1.10

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-166365976-G-A is Benign according to our data. Variant chr6-166365976-G-A is described in ClinVar as [Benign]. Clinvar id is 138241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPC1	NM_016098.4 linkuse as main transcript	c.303C>T	p.His101=	splice_region_variant, synonymous_variant	4/5	ENST00000360961.11	NP_057182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPC1	ENST00000360961.11 linkuse as main transcript	c.303C>T	p.His101=	splice_region_variant, synonymous_variant	4/5	5	NM_016098.4	ENSP00000354223	P3

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6070

AN:

152102

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0104

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0325

Gnomad ASJ

AF:

0.0507

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0782

Gnomad FIN

AF:

0.0544

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0563

Gnomad OTH

AF:

0.0480

GnomAD3 exomes

AF:

0.0486

AC:

12147

AN:

250058

Hom.:

404

AF XY:

0.0523

AC XY:

7073

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.00832

Gnomad AMR exome

AF:

0.0251

Gnomad ASJ exome

AF:

0.0433

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0841

Gnomad FIN exome

AF:

0.0567

Gnomad NFE exome

AF:

0.0587

Gnomad OTH exome

AF:

0.0458

GnomAD4 exome

AF:

0.0547

AC:

79762

AN:

1459370

Hom.:

2497

Cov.:

AF XY:

0.0558

AC XY:

40539

AN XY:

725968

show subpopulations

Gnomad4 AFR exome

AF:

0.00869

Gnomad4 AMR exome

AF:

0.0265

Gnomad4 ASJ exome

AF:

0.0433

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0876

Gnomad4 FIN exome

AF:

0.0572

Gnomad4 NFE exome

AF:

0.0566

Gnomad4 OTH exome

AF:

0.0534

GnomAD4 genome

AF:

0.0399

AC:

6069

AN:

152220

Hom.:

165

Cov.:

AF XY:

0.0410

AC XY:

3051

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0103

Gnomad4 AMR

AF:

0.0324

Gnomad4 ASJ

AF:

0.0507

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0782

Gnomad4 FIN

AF:

0.0544

Gnomad4 NFE

AF:

0.0564

Gnomad4 OTH

AF:

0.0475

Alfa

AF:

0.0513

Hom.:

429

Bravo

AF:

0.0372

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Feb 22, 2016	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2013

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.1

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0014

dbscSNV1_RF

Benign

0.068

SpliceAI score (max)

0.040

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