rs2682547

Variant names:

• chr19-43496905-T-A
• rs2682547
• ENST00000599242.1:c.*198A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-43496905-T-A
• chr19-43496905-T-C
• chr19-43496905-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000599242.1(PHLDB3):​c.*198A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000179 in 558,502 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: PHLDB3 ENST00000599242.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHLDB3	NM_198850.4	c.825+213A>T		intron_variant	Intron 6 of 15	ENST00000292140.10	NP_942147.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHLDB3	ENST00000599242.1	c.*198A>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000471158.1
PHLDB3	ENST00000292140.10	c.825+213A>T		intron_variant	Intron 6 of 15	5	NM_198850.4	ENSP00000292140.5
PHLDB3	ENST00000600660.1	c.243+213A>T		intron_variant	Intron 2 of 5	3		ENSP00000473000.1
PHLDB3	ENST00000596141.2	n.825+213A>T		intron_variant	Intron 5 of 13	3		ENSP00000469372.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000179 AC: 1 AN: 558502 Hom.: 0 Cov.: 8 AF XY: 0.00000368 AC XY: 1 AN XY: 271866

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 12822

American (AMR) AF: 0.00 AC: 0 AN: 7792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11112

East Asian (EAS) AF: 0.00 AC: 0 AN: 24068

South Asian (SAS) AF: 0.00 AC: 0 AN: 8248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1902

European-Non Finnish (NFE) AF: 0.00000225 AC: 1 AN: 444822

Other (OTH) AF: 0.00 AC: 0 AN: 26672

⚠️ 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.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 20545

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.033
DANN	Benign	0.56
PhyloP100		-1.7

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: rs2682547; hg19: chr19-44001057;