12-76033699-T-C

Position:

• chr12-76033699-T-C

Variant summary

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

The ENST00000547721.1(PHLDA1-DT):​n.581T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,156 control chromosomes in the GnomAD database, including 2,469 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 0.17 (2469 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PHLDA1-DT ENST00000547721.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

Genes affected

PHLDA1-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHLDA1-DT	NR_185978.1	n.1426T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHLDA1-DT	ENST00000547721.1	n.581T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26579 AN: 152036 Hom.: 2469 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.0354

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.208

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.175 AC: 26591 AN: 152156 Hom.: 2469 Cov.: 32 AF XY: 0.175 AC XY: 13024 AN XY: 74388

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.0357

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.207

Alfa AF: 0.200 Hom.: 3737

Bravo AF: 0.173

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.3
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2082529; hg19: chr12-76427479;