chr19-43479588-T-G

Position:

• chr19-43479588-T-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_198850.4(PHLDB3):​c.1491A>C​(p.Pro497=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 16)
  • Exomes 𝑓: 0.013 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: PHLDB3 NM_198850.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.46

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 19-43479588-T-G is Benign according to our data. Variant chr19-43479588-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 791658.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.46 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHLDB3	NM_198850.4	c.1491A>C	p.Pro497=	synonymous_variant	14/16	ENST00000292140.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHLDB3	ENST00000292140.10	c.1491A>C	p.Pro497=	synonymous_variant	14/16	5	NM_198850.4	P1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 49 AN: 128610 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00135

Gnomad AMR AF: 0.000405

Gnomad ASJ AF: 0.00102

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.000267

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000310

Gnomad OTH AF: 0.000579

GnomAD3 exomes AF: 0.00738 AC: 897 AN: 121486 Hom.: 2 AF XY: 0.00727 AC XY: 482 AN XY: 66272

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.00908

Gnomad ASJ exome AF: 0.00410

Gnomad EAS exome AF: 0.00756

Gnomad SAS exome AF: 0.00997

Gnomad FIN exome AF: 0.00217

Gnomad NFE exome AF: 0.00610

Gnomad OTH exome AF: 0.00951

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0134 AC: 6963 AN: 519244 Hom.: 2 Cov.: 7 AF XY: 0.0139 AC XY: 3811 AN XY: 273318

Gnomad4 AFR exome AF: 0.0167

Gnomad4 AMR exome AF: 0.0195

Gnomad4 ASJ exome AF: 0.00863

Gnomad4 EAS exome AF: 0.00846

Gnomad4 SAS exome AF: 0.0269

Gnomad4 FIN exome AF: 0.00610

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.000381 AC: 49 AN: 128694 Hom.: 0 Cov.: 16 AF XY: 0.000386 AC XY: 24 AN XY: 62234

Gnomad4 AFR AF: 0.000386

Gnomad4 AMR AF: 0.000405

Gnomad4 ASJ AF: 0.00102

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.000267

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000310

Gnomad4 OTH AF: 0.000574

Alfa AF: 0.00122 Hom.: 10250

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.90
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1133929; hg19: chr19-43983740;