19-43478092-C-G

Position:

• chr19-43478092-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198850.4(PHLDB3):​c.1743G>C​(p.Gln581His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PHLDB3 NM_198850.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDB3	NM_198850.4	c.1743G>C	p.Gln581His	missense_variant	15/16	ENST00000292140.10	NP_942147.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDB3	ENST00000292140.10	c.1743G>C	p.Gln581His	missense_variant	15/16	5	NM_198850.4	ENSP00000292140.5
PHLDB3	ENST00000595498.5	n.890G>C		non_coding_transcript_exon_variant	9/10	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2024

The c.1743G>C (p.Q581H) alteration is located in exon 15 (coding exon 14) of the PHLDB3 gene. This alteration results from a G to C substitution at nucleotide position 1743, causing the glutamine (Q) at amino acid position 581 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.1	M
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.64		Gain of sheet (P = 0.1208);
MVP		0.77
MPC		0.51
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.81
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-43982244;