rs9618

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-167924521-G-A
• chr1-167924521-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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

GnomAD2 exomes AF: 0.360 AC: 76094 AN: 211362 AF XY: 0.347

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 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

African (AFR) AF: 0.612 AC: 18782 AN: 30666

American (AMR) AF: 0.547 AC: 20193 AN: 36900

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 8922 AN: 24706

East Asian (EAS) AF: 0.189 AC: 7260 AN: 38386

South Asian (SAS) AF: 0.258 AC: 20285 AN: 78688

European-Finnish (FIN) AF: 0.364 AC: 19013 AN: 52204

Middle Eastern (MID) AF: 0.382 AC: 2089 AN: 5472

European-Non Finnish (NFE) AF: 0.341 AC: 371181 AN: 1087212

Other (OTH) AF: 0.346 AC: 20127 AN: 58124

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

African (AFR) AF: 0.607 AC: 24989 AN: 41142

American (AMR) AF: 0.518 AC: 7852 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1252 AN: 3452

East Asian (EAS) AF: 0.194 AC: 995 AN: 5126

South Asian (SAS) AF: 0.259 AC: 1228 AN: 4750

European-Finnish (FIN) AF: 0.376 AC: 3867 AN: 10288

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.342 AC: 23105 AN: 67594

Other (OTH) AF: 0.404 AC: 844 AN: 2090

Alfa AF: 0.376 Hom.: 13287

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
PhyloP100		2.0
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

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