rs10409591

Positions:

• chr19-43482703-G-A
• chr19-43482703-G-C
• chr19-43482703-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198850.4(PHLDB3):​c.1486-3110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,822 control chromosomes in the GnomAD database, including 11,183 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11183 hom., cov: 31)
• Consequence: PHLDB3 NM_198850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.931

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLDB3	NM_198850.4	c.1486-3110C>T		intron_variant		ENST00000292140.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLDB3	ENST00000292140.10	c.1486-3110C>T		intron_variant		5	NM_198850.4	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57629 AN: 151704 Hom.: 11173 Cov.: 31

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.381

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.380 AC: 57679 AN: 151822 Hom.: 11183 Cov.: 31 AF XY: 0.379 AC XY: 28111 AN XY: 74226

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.383

Alfa AF: 0.202 Hom.: 408

Bravo AF: 0.378

Asia WGS AF: 0.508 AC: 1765 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs10409591; hg19: chr19-43986855;