chr12-76031257-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000266671.10(PHLDA1):​c.485G>T​(p.Gly162Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PHLDA1
ENST00000266671.10 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.71

Publications

0 publications found
Variant links:
Genes affected
PHLDA1 (HGNC:8933): (pleckstrin homology like domain family A member 1) This gene encodes an evolutionarily conserved proline-histidine rich nuclear protein. The encoded protein may play an important role in the anti-apoptotic effects of insulin-like growth factor-1. [provided by RefSeq, Jul 2008]
PHLDA1-AS1 (HGNC:55461): (PHLDA1 antisense RNA 1)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PHLDA1NM_007350.3 linkc.485G>T p.Gly162Val missense_variant Exon 1 of 2 NP_031376.3 Q8WV24
PHLDA1-AS1NR_186034.1 linkn.448C>A non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PHLDA1ENST00000266671.10 linkc.485G>T p.Gly162Val missense_variant Exon 1 of 2 1 ENSP00000266671.5 Q8WV24
PHLDA1ENST00000602540.5 linkc.62G>T p.Gly21Val missense_variant Exon 1 of 2 1 ENSP00000473593.1 R4GND3
PHLDA1-AS1ENST00000552367.1 linkn.448C>A non_coding_transcript_exon_variant Exon 2 of 2 4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 05, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.485G>T (p.G162V) alteration is located in exon 1 (coding exon 1) of the PHLDA1 gene. This alteration results from a G to T substitution at nucleotide position 485, causing the glycine (G) at amino acid position 162 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
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
.;T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Benign
0.56
D
LIST_S2
Uncertain
0.94
D;D;.
M_CAP
Pathogenic
0.30
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.2
.;M;M
PhyloP100
4.7
PrimateAI
Pathogenic
0.86
D
PROVEAN
Uncertain
-4.3
.;.;D
REVEL
Benign
0.25
Sift
Uncertain
0.0010
.;.;D
Sift4G
Uncertain
0.010
D;D;D
Polyphen
0.99
.;D;D
Vest4
0.73
MutPred
0.32
.;Loss of disorder (P = 0.0351);Loss of disorder (P = 0.0351);
MVP
0.86
MPC
1.8
ClinPred
1.0
D
GERP RS
4.4
PromoterAI
0.10
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.83
gMVP
0.78
Mutation Taster
=36/64
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

hg19: chr12-76425037; API