6-166366190-T-C

Position:

• chr6-166366190-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016098.4(MPC1):​c.173-84A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,429,934 control chromosomes in the GnomAD database, including 200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (110 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (90 hom.)
• Consequence: MPC1 NM_016098.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.843

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-166366190-T-C is Benign according to our data. Variant chr6-166366190-T-C is described in ClinVar as [Benign]. Clinvar id is 1298151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPC1	NM_016098.4	c.173-84A>G		intron_variant		ENST00000360961.11	NP_057182.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPC1	ENST00000360961.11	c.173-84A>G		intron_variant		5	NM_016098.4	ENSP00000354223.6

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3118 AN: 152090 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00240 AC: 3067 AN: 1277726 Hom.: 90 AF XY: 0.00217 AC XY: 1356 AN XY: 626198

Gnomad4 AFR exome AF: 0.0728

Gnomad4 AMR exome AF: 0.00553

Gnomad4 ASJ exome AF: 0.00399

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000147

Gnomad4 FIN exome AF: 0.0000519

Gnomad4 NFE exome AF: 0.000371

Gnomad4 OTH exome AF: 0.00577

GnomAD4 genome AF: 0.0206 AC: 3136 AN: 152208 Hom.: 110 Cov.: 33 AF XY: 0.0211 AC XY: 1569 AN XY: 74428

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0178 Hom.: 9

Bravo AF: 0.0238

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.87
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs116140938; hg19: chr6-166779678;