6-125253363-T-C

Position:

• chr6-125253363-T-C

Variant summary

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

The NM_003287.4(TPD52L1):​c.387-354T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 264,786 control chromosomes in the GnomAD database, including 22,423 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 0.39 (12152 hom., cov: 32)
  • Exomes 𝑓: 0.41 (10271 hom.)
• Consequence: TPD52L1 NM_003287.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

Genes affected

TPD52L1 (HGNC:12006): (TPD52 like 1) This gene encodes a member of a family of proteins that contain coiled-coil domains and may form hetero- or homomers. The encoded protein is involved in cell proliferation and calcium signaling. It also interacts with the mitogen-activated protein kinase kinase kinase 5 (MAP3K5/ASK1) and positively regulates MAP3K5-induced apoptosis. Multiple alternatively spliced transcript variants have been observed. [provided by RefSeq, Jan 2016]

HDDC2 (HGNC:21078): (HD domain containing 2) Predicted to enable 5'-deoxynucleotidase activity. Predicted to be involved in dephosphorylation. Predicted to be active in cytoplasm. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPD52L1	NM_003287.4	c.387-354T>C		intron_variant		ENST00000534000.6	NP_003278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPD52L1	ENST00000534000.6	c.387-354T>C		intron_variant		1	NM_003287.4	ENSP00000434142	P3

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59847 AN: 151868 Hom.: 12135 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.410 AC: 46241 AN: 112800 Hom.: 10271 Cov.: 0 AF XY: 0.414 AC XY: 24207 AN XY: 58508

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.626

Gnomad4 SAS exome AF: 0.539

Gnomad4 FIN exome AF: 0.369

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.394 AC: 59899 AN: 151986 Hom.: 12152 Cov.: 32 AF XY: 0.401 AC XY: 29787 AN XY: 74270

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.613

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.392

Alfa AF: 0.380 Hom.: 15480

Bravo AF: 0.402

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.86

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: rs3799732; hg19: chr6-125574509;