chr6-125253363-T-C

Variant names:

• chr6-125253363-T-C
• rs3799732
• NM_003287.4:c.387-354T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003287.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L1	NM_003287.4	MANE Select	c.387-354T>C		intron	N/A	NP_003278.1
	TPD52L1	NM_001318903.2		c.402-354T>C		intron	N/A	NP_001305832.1
	TPD52L1	NM_001300994.3		c.387-3735T>C		intron	N/A	NP_001287923.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L1	ENST00000534000.6	TSL:1 MANE Select	c.387-354T>C		intron	N/A	ENSP00000434142.1
	TPD52L1	ENST00000368402.9	TSL:1	c.387-354T>C		intron	N/A	ENSP00000357387.5
	TPD52L1	ENST00000368388.6	TSL:1	c.386+4980T>C		intron	N/A	ENSP00000357373.2

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

African (AFR) AF: 0.384 AC: 1271 AN: 3312

American (AMR) AF: 0.545 AC: 2749 AN: 5046

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1322 AN: 3602

East Asian (EAS) AF: 0.626 AC: 4720 AN: 7542

South Asian (SAS) AF: 0.539 AC: 4978 AN: 9236

European-Finnish (FIN) AF: 0.369 AC: 1838 AN: 4986

Middle Eastern (MID) AF: 0.410 AC: 218 AN: 532

European-Non Finnish (NFE) AF: 0.369 AC: 26441 AN: 71716

Other (OTH) AF: 0.396 AC: 2704 AN: 6828

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

African (AFR) AF: 0.381 AC: 15794 AN: 41456

American (AMR) AF: 0.496 AC: 7585 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1218 AN: 3464

East Asian (EAS) AF: 0.613 AC: 3162 AN: 5162

South Asian (SAS) AF: 0.542 AC: 2605 AN: 4810

European-Finnish (FIN) AF: 0.354 AC: 3742 AN: 10556

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.362 AC: 24590 AN: 67946

Other (OTH) AF: 0.392 AC: 825 AN: 2106

Alfa AF: 0.379 Hom.: 18206

Bravo AF: 0.402

Asia WGS AF: 0.527 AC: 1831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.7
DANN	Benign	0.86
PhyloP100		0.026
Mutation Taster		=100/0	polymorphism (auto)

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: rs3799732; hg19: chr6-125574509;