10-120513975-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001030059.3(PLPP4):ā€‹c.230A>Cā€‹(p.Lys77Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,888 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

PLPP4
NM_001030059.3 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47
Variant links:
Genes affected
PLPP4 (HGNC:23531): (phospholipid phosphatase 4) Enables diacylglycerol diphosphate phosphatase activity; identical protein binding activity; and phosphatidate phosphatase activity. Involved in phospholipid dephosphorylation and regulation of calcium ion import. Predicted to be located in plasma membrane. Biomarker of breast cancer. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2743106).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLPP4NM_001030059.3 linkc.230A>C p.Lys77Thr missense_variant 3/7 ENST00000398250.6 NP_001025230.1 Q5VZY2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLPP4ENST00000398250.6 linkc.230A>C p.Lys77Thr missense_variant 3/71 NM_001030059.3 ENSP00000381302.1 Q5VZY2-1
PLPP4ENST00000369073.3 linkn.200A>C non_coding_transcript_exon_variant 3/75

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461692
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
727166
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000126
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 GeneticsJul 26, 2021The c.230A>C (p.K77T) alteration is located in exon 3 (coding exon 3) of the PLPP4 gene. This alteration results from a A to C substitution at nucleotide position 230, causing the lysine (K) at amino acid position 77 to be replaced by a threonine (T). 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
0.18
BayesDel_addAF
Uncertain
0.048
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.074
T;.;.
Eigen
Benign
-0.017
Eigen_PC
Benign
0.16
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.92
D;D;D
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.27
T;T;T
MetaSVM
Benign
-0.63
T
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-2.0
N;N;N
REVEL
Uncertain
0.34
Sift
Benign
0.30
T;T;T
Sift4G
Benign
0.38
T;T;T
Polyphen
0.0020
B;.;.
Vest4
0.60
MutPred
0.50
Gain of catalytic residue at K77 (P = 0.0064);Gain of catalytic residue at K77 (P = 0.0064);.;
MVP
0.68
MPC
0.43
ClinPred
0.46
T
GERP RS
5.7
Varity_R
0.093
gMVP
0.84

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: rs1267407483; hg19: chr10-122273487; API