Variant chr19-43479472-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198850.4(PHLDB3):c.1607G>A(p.Arg536His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,562,122 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

PHLDB3
NM_198850.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

PHLDB3 (HGNC:30499): (pleckstrin homology like domain family B member 3) Enables enzyme binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PHLDB3 links:

PHLDB3 (HGNC:):

PHLDB3 links:

Genome browser will be placed here

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
PHLDB3	NM_198850.4 linkuse as main transcript	c.1607G>A	p.Arg536His	missense_variant	14/16	ENST00000292140.10	NP_942147.3	Q6NSJ2-1Q96HZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB3	ENST00000292140.10 linkuse as main transcript	c.1607G>A	p.Arg536His	missense_variant	14/16	5	NM_198850.4	ENSP00000292140.5		Q6NSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

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:

0.000190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000135

AC:

AN:

170314

Hom.:

AF XY:

0.000187

AC XY:

AN XY:

90988

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:

0.000128

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.000433

GnomAD4 exome

AF:

0.000390

AC:

550

AN:

1410496

Hom.:

Cov.:

AF XY:

0.000370

AC XY:

258

AN XY:

696818

show subpopulations

Gnomad4 AFR exome

AF:

0.0000935

Gnomad4 AMR exome

AF:

0.0000271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000113

Gnomad4 FIN exome

AF:

0.000101

Gnomad4 NFE exome

AF:

0.000461

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.000178

AC:

AN:

151626

Hom.:

Cov.:

AF XY:

0.000203

AC XY:

AN XY:

74042

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.000324

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000227

Hom.:

Bravo

AF:

0.000178

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.0000868

AC:

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

Aug 01, 2024

The c.1607G>A (p.R536H) alteration is located in exon 14 (coding exon 13) of the PHLDB3 gene. This alteration results from a G to A substitution at nucleotide position 1607, causing the arginine (R) at amino acid position 536 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.92

D;T

M_CAP

Benign

0.079

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.2

D;.

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

D;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;.

Vest4

0.38

MVP

0.79

MPC

0.59

ClinPred

0.54

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.39

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