19-43479588-T-C

Variant names:

• chr19-43479588-T-C
• rs1133929
• NM_198850.4:c.1491A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_198850.4(PHLDB3):​c.1491A>G​(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: 𝑓 0.78 (36963 hom., cov: 16)
  • Exomes 𝑓: 0.74 (129901 hom.)
• Consequence: PHLDB3 NM_198850.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.46 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.780 AC: 100221 AN: 128534 Hom.: 36915 Cov.: 16

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.725

Gnomad OTH AF: 0.769

GnomAD2 exomes AF: 0.725 AC: 88120 AN: 121486 AF XY: 0.720

Gnomad AFR exome AF: 0.868

Gnomad AMR exome AF: 0.768

Gnomad ASJ exome AF: 0.677

Gnomad EAS exome AF: 0.783

Gnomad FIN exome AF: 0.718

Gnomad NFE exome AF: 0.686

Gnomad OTH exome AF: 0.709

GnomAD4 exome AF: 0.738 AC: 384350 AN: 520902 Hom.: 129901 Cov.: 7 AF XY: 0.735 AC XY: 201643 AN XY: 274264

African (AFR) AF: 0.869 AC: 13578 AN: 15622

American (AMR) AF: 0.750 AC: 21717 AN: 28952

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 11594 AN: 16600

East Asian (EAS) AF: 0.792 AC: 22651 AN: 28600

South Asian (SAS) AF: 0.728 AC: 39705 AN: 54554

European-Finnish (FIN) AF: 0.748 AC: 31440 AN: 42038

Middle Eastern (MID) AF: 0.719 AC: 1448 AN: 2014

European-Non Finnish (NFE) AF: 0.727 AC: 222512 AN: 305948

Other (OTH) AF: 0.742 AC: 19705 AN: 26574

GnomAD4 genome AF: 0.780 AC: 100307 AN: 128618 Hom.: 36963 Cov.: 16 AF XY: 0.780 AC XY: 48519 AN XY: 62188

African (AFR) AF: 0.888 AC: 32242 AN: 36296

American (AMR) AF: 0.754 AC: 9306 AN: 12338

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2086 AN: 2940

East Asian (EAS) AF: 0.781 AC: 3343 AN: 4278

South Asian (SAS) AF: 0.765 AC: 2860 AN: 3740

European-Finnish (FIN) AF: 0.770 AC: 6339 AN: 8236

Middle Eastern (MID) AF: 0.712 AC: 185 AN: 260

European-Non Finnish (NFE) AF: 0.725 AC: 42072 AN: 58052

Other (OTH) AF: 0.768 AC: 1337 AN: 1740

Alfa AF: 0.667 Hom.: 11581

Bravo AF: 0.728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.89
DANN	Benign	0.40
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1133929; hg19: chr19-43983740; COSMIC: COSV52670241;