dbSNP rs1133929: PHLDB3:p.Pro497Pro (chr19-43479588-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_198850.4(PHLDB3):c.1491A>T(p.Pro497Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P497P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 16)

Exomes 𝑓: 0.0000019 ( 0 hom. )

Consequence

PHLDB3
NM_198850.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.46

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP7

Synonymous conserved (PhyloP=-2.46 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB3	NM_198850.4 link	c.1491A>T	p.Pro497Pro	synonymous_variant	Exon 14 of 16	ENST00000292140.10	NP_942147.3	Q6NSJ2-1Q96HZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB3	ENST00000292140.10 link	c.1491A>T	p.Pro497Pro	synonymous_variant	Exon 14 of 16	5	NM_198850.4	ENSP00000292140.5		Q6NSJ2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000192

AC:

AN:

521902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

274794

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

15644

American (AMR)

AF:

0.00

AC:

AN:

29004

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16638

East Asian (EAS)

AF:

0.00

AC:

AN:

28638

South Asian (SAS)

AF:

0.00

AC:

AN:

54622

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2016

European-Non Finnish (NFE)

AF:

0.00000326

AC:

AN:

306608

Other (OTH)

AF:

0.00

AC:

AN:

26630

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.84

(source)

DANN

Benign

0.47

PhyloP100

-2.5

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over