dbSNP rs2420: MPC2:c.*1059T>A (chr1-167917264-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001143674.4(MPC2):c.*1059T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,090 control chromosomes in the GnomAD database, including 3,827 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 0.20 ( 3827 hom., cov: 32)

Exomes 𝑓: 0.33 ( 0 hom. )

Consequence

MPC2
NM_001143674.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.288

Publications

10 publications found

Variant links:

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]

MPC2 links:

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]

DCAF6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143674.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPC2	NM_001143674.4	MANE Select	c.*1059T>A	3_prime_UTR	Exon 6 of 6	NP_001137146.1	O95563
MPC2	NM_015415.3		c.*1059T>A	3_prime_UTR	Exon 6 of 6	NP_056230.1	O95563
MPC2	NR_026550.3		n.1598T>A	non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPC2	ENST00000271373.9	TSL:1 MANE Select	c.*1059T>A		3_prime_UTR	Exon 6 of 6	ENSP00000271373.4	O95563
	MPC2	ENST00000367846.8	TSL:1	c.*1059T>A		3_prime_UTR	Exon 5 of 5	ENSP00000356820.4	O95563

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30827

AN:

151960

Hom.:

3824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0811

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.135

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.333

AC:

AN:

Hom.:

Cov.:

AF XY:

0.300

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.203

AC:

30839

AN:

152078

Hom.:

3827

Cov.:

AF XY:

0.204

AC XY:

15173

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.0809

AC:

3361

AN:

41540

American (AMR)

AF:

0.364

AC:

5544

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

811

AN:

3468

East Asian (EAS)

AF:

0.136

AC:

703

AN:

5176

South Asian (SAS)

AF:

0.186

AC:

897

AN:

4812

European-Finnish (FIN)

AF:

0.209

AC:

2201

AN:

10546

Middle Eastern (MID)

AF:

0.269

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16464

AN:

67968

Other (OTH)

AF:

0.218

AC:

461

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1192

2383

3575

4766

5958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.222

Hom.:

560

Bravo

AF:

0.213

Asia WGS

AF:

0.158

AC:

552

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

(source)

DANN

Benign

0.43

PhyloP100

-0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over