Genetic Variant NM_198850.4:c.1491A>T (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:

Genome browser will be placed here

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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