6-166365191-T-G

Position:

• chr6-166365191-T-G

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.*238A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 374,584 control chromosomes in the GnomAD database, including 35,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (12119 hom., cov: 33)
  • Exomes 𝑓: 0.45 (23310 hom.)
• Consequence: MPC1 NM_016098.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 6-166365191-T-G is Benign according to our data. Variant chr6-166365191-T-G is described in ClinVar as [Benign]. Clinvar id is 1221336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPC1	NM_016098.4	c.*238A>C		3_prime_UTR_variant	5/5	ENST00000360961.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPC1	ENST00000360961.11	c.*238A>C		3_prime_UTR_variant	5/5	5	NM_016098.4	P3
MPC1	ENST00000621630.1	c.*238A>C		3_prime_UTR_variant	5/5	5		A1
MPC1	ENST00000487218.5	n.801A>C		non_coding_transcript_exon_variant	6/6	5
MPC1	ENST00000366868.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56142 AN: 151986 Hom.: 12109 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.369

GnomAD4 exome AF: 0.450 AC: 100207 AN: 222480 Hom.: 23310 Cov.: 3 AF XY: 0.451 AC XY: 51460 AN XY: 114038

Gnomad4 AFR exome AF: 0.138

Gnomad4 AMR exome AF: 0.471

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.702

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.440

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.369 AC: 56160 AN: 152104 Hom.: 12119 Cov.: 33 AF XY: 0.380 AC XY: 28282 AN XY: 74358

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.670

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.434

Gnomad4 OTH AF: 0.373

Alfa AF: 0.423 Hom.: 17788

Bravo AF: 0.351

Asia WGS AF: 0.636 AC: 2204 AN: 3472

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

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs3728; hg19: chr6-166778679; COSMIC: COSV59132834; COSMIC: COSV59132834;