Variant chr1-167935811-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001143674.4(MPC2):c.31G>C(p.Ala11Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000641 in 1,403,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

MPC2
NM_001143674.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.42

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:

DCAF6 (HGNC:):

DCAF6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPC2	NM_001143674.4 linkuse as main transcript	c.31G>C	p.Ala11Pro	missense_variant	2/6	ENST00000271373.9	NP_001137146.1	O95563A0A024R8Z5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MPC2	ENST00000271373.9 linkuse as main transcript	c.31G>C	p.Ala11Pro	missense_variant	2/6	1	NM_001143674.4	ENSP00000271373.4	O95563
MPC2	ENST00000367846.8 linkuse as main transcript	c.31G>C	p.Ala11Pro	missense_variant	1/5	1		ENSP00000356820.4	O95563
MPC2	ENST00000458574.1 linkuse as main transcript	c.31G>C	p.Ala11Pro	missense_variant	2/5	5		ENSP00000392874.1	Q5R3B4
DCAF6	ENST00000450548.5 linkuse as main transcript	n.29C>G		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

162236

Hom.:

AF XY:

0.00

AC XY:

AN XY:

85942

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000838

Gnomad SAS exome

AF:

0.0000430

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000641

AC:

AN:

1403762

Hom.:

Cov.:

AF XY:

0.00000577

AC XY:

AN XY:

693074

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000753

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.24e-7

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000888

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

The c.31G>C (p.A11P) alteration is located in exon 2 (coding exon 1) of the MPC2 gene. This alteration results from a G to C substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.83

.;T;T

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.73

D;D;D

MetaSVM

Benign

-0.29

MutationAssessor

Uncertain

2.7

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.8

N;N;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.040

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.61

MutPred

0.50

Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);Loss of helix (P = 0.0041);

MVP

0.47

MPC

0.94

ClinPred

0.90

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.81

gMVP

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over