chr14-24096930-C-T

Variant summary

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

The ENST00000216780.9(PCK2):​c.68C>T​(p.Ser23Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCK2
ENST00000216780.9 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.769
Variant links:
Genes affected
PCK2 (HGNC:8725): (phosphoenolpyruvate carboxykinase 2, mitochondrial) This gene encodes a mitochondrial enzyme that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in the presence of guanosine triphosphate (GTP). A cytosolic form of this protein is encoded by a different gene and is the key enzyme of gluconeogenesis in the liver. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2014]
NRL (HGNC:8002): (neural retina leucine zipper) This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008]

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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=0.08427569).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCK2NM_004563.4 linkuse as main transcriptc.68C>T p.Ser23Leu missense_variant 2/10 ENST00000216780.9 NP_004554.3
NRLNM_001354768.3 linkuse as main transcriptc.-27-14055G>A intron_variant ENST00000561028.6 NP_001341697.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCK2ENST00000216780.9 linkuse as main transcriptc.68C>T p.Ser23Leu missense_variant 2/101 NM_004563.4 ENSP00000216780 P1Q16822-1
NRLENST00000561028.6 linkuse as main transcriptc.-27-14055G>A intron_variant 2 NM_001354768.3 ENSP00000454062 P1P54845-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
250952
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135654
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461260
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726988
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
12
DANN
Uncertain
0.98
DEOGEN2
Benign
0.010
T;T;.
Eigen
Benign
-0.88
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.37
N
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.084
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.34
.;N;N
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.40
N;N;N
REVEL
Benign
0.031
Sift
Benign
0.053
T;T;T
Sift4G
Benign
0.081
T;T;T
Polyphen
0.0080, 0.0
.;B;B
Vest4
0.13
MutPred
0.39
.;Loss of helix (P = 0.0237);Loss of helix (P = 0.0237);
MVP
0.32
MPC
0.054
ClinPred
0.091
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.085
gMVP
0.56

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: rs61752842; hg19: chr14-24566139; COSMIC: COSV53748792; COSMIC: COSV53748792; API