chr12-102197709-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002674.4(PMCH):​c.62G>T​(p.Gly21Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000056 in 1,606,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

PMCH
NM_002674.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
Variant links:
Genes affected
PMCH (HGNC:9109): (pro-melanin concentrating hormone) This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include melanin-concentrating hormone (MCH), neuropeptide-glutamic acid-isoleucine (NEI), and neuropeptide-glycine-glutamic acid (NGE). Melanin-concentrating hormone is a 19-amino acid neuropeptide that stimulates hunger and may additionally regulate energy homeostasis, reproductive function, and sleep. Pseudogenes of this gene have been identified on chromosome 5. [provided by RefSeq, Jul 2015]
HELLPAR (HGNC:43984): (HELLP associated long non-coding RNA)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.069850236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PMCHNM_002674.4 linkuse as main transcriptc.62G>T p.Gly21Val missense_variant 1/3 ENST00000329406.5
PMCHXM_017019483.3 linkuse as main transcriptc.62G>T p.Gly21Val missense_variant 1/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PMCHENST00000329406.5 linkuse as main transcriptc.62G>T p.Gly21Val missense_variant 1/31 NM_002674.4 P1
HELLPARENST00000626826.1 linkuse as main transcriptn.125C>A non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0000594
AC:
9
AN:
151510
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00231
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000927
AC:
23
AN:
248050
Hom.:
0
AF XY:
0.0000893
AC XY:
12
AN XY:
134410
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00201
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000557
AC:
81
AN:
1454498
Hom.:
0
Cov.:
29
AF XY:
0.0000566
AC XY:
41
AN XY:
723932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00212
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000136
Gnomad4 OTH exome
AF:
0.000167
GnomAD4 genome
AF:
0.0000594
AC:
9
AN:
151510
Hom.:
0
Cov.:
32
AF XY:
0.0000405
AC XY:
3
AN XY:
74004
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00231
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000148
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000203
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000289
AC:
2
AN:
3476
EpiCase
AF:
0.0000547
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsJun 30, 2022The c.62G>T (p.G21V) alteration is located in exon 1 (coding exon 1) of the PMCH gene. This alteration results from a G to T substitution at nucleotide position 62, causing the glycine (G) at amino acid position 21 to be replaced by a valine (V). 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
Benign
0.15
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.27
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-0.81
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.18
Sift
Benign
0.11
T
Sift4G
Benign
0.17
T
Polyphen
0.91
P
Vest4
0.40
MVP
0.80
MPC
0.072
ClinPred
0.13
T
GERP RS
4.2
Varity_R
0.35
gMVP
0.33

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.

Other links and lift over

dbSNP: rs771909727; hg19: chr12-102591487; API