NM_001143674.4:c.126C>T

Variant names:

• chr1-167924521-G-A
• rs9618
• NM_001143674.4:c.126C>T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001143674.4(MPC2):​c.126C>T​(p.Phe42Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,563,170 control chromosomes in the GnomAD database, including 103,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15070 hom., cov: 30)
  • Exomes 𝑓: 0.35 (87938 hom.)
• Consequence: MPC2 NM_001143674.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

Genes affected

MPC2 (HGNC:24515): (mitochondrial pyruvate carrier 2) Enables identical protein binding activity. Predicted to be involved in mitochondrial pyruvate transmembrane transport. Predicted to act upstream of or within mitochondrial acetyl-CoA biosynthetic process from pyruvate and positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

DCAF6 (HGNC:30002): (DDB1 and CUL4 associated factor 6) The protein encoded by this gene is a ligand-dependent coactivator of nuclear receptors, including nuclear receptor subfamily 3 group C member 1 (NR3C1), glucocorticoid receptor (GR), and androgen receptor (AR). The encoded protein and DNA damage binding protein 2 (DDB2) may act as tumor promoters and tumor suppressors, respectively, by regulating the level of androgen receptor in prostate tissues. In addition, this protein can act with glucocorticoid receptor to promote human papillomavirus gene expression. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=1.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPC2	NM_001143674.4	c.126C>T	p.Phe42Phe	synonymous_variant	Exon 3 of 6	ENST00000271373.9	NP_001137146.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPC2	ENST00000271373.9	c.126C>T	p.Phe42Phe	synonymous_variant	Exon 3 of 6	1	NM_001143674.4	ENSP00000271373.4
MPC2	ENST00000367846.8	c.126C>T	p.Phe42Phe	synonymous_variant	Exon 2 of 5	1		ENSP00000356820.4
MPC2	ENST00000458574.1	c.126C>T	p.Phe42Phe	synonymous_variant	Exon 3 of 5	5		ENSP00000392874.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64550 AN: 150696 Hom.: 15039 Cov.: 30

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.360 AC: 76094 AN: 211362 Hom.: 15078 AF XY: 0.347 AC XY: 39905 AN XY: 115090

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.556

Gnomad ASJ exome AF: 0.357

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.245

Gnomad FIN exome AF: 0.367

Gnomad NFE exome AF: 0.331

Gnomad OTH exome AF: 0.366

GnomAD4 exome AF: 0.345 AC: 487852 AN: 1412358 Hom.: 87938 Cov.: 29 AF XY: 0.342 AC XY: 240209 AN XY: 701996

Gnomad4 AFR exome AF: 0.612

Gnomad4 AMR exome AF: 0.547

Gnomad4 ASJ exome AF: 0.361

Gnomad4 EAS exome AF: 0.189

Gnomad4 SAS exome AF: 0.258

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.429 AC: 64634 AN: 150812 Hom.: 15070 Cov.: 30 AF XY: 0.429 AC XY: 31570 AN XY: 73576

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.404

Alfa AF: 0.360 Hom.: 9171

Bravo AF: 0.448

Asia WGS AF: 0.249 AC: 863 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.9
DANN	Benign	0.83

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: rs9618; hg19: chr1-167893759; COSMIC: COSV54796610;