Genetic Variant TPD52L1:c.387-354T>C (chr6-125253363-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260

Publications

12 publications found

Variant links:

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]

TPD52L1 links:

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]

HDDC2 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L1	NM_003287.4 link	c.387-354T>C		intron_variant	Intron 4 of 6	ENST00000534000.6	NP_003278.1	Q16890-1Q15730

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52L1	ENST00000534000.6 link	c.387-354T>C		intron_variant	Intron 4 of 6	1	NM_003287.4	ENSP00000434142.1		Q16890-1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59847

AN:

151868

Hom.:

12135

Cov.:

show subpopulations

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.:

AF XY:

0.414

AC XY:

24207

AN XY:

58508

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

1276

2552

3829

5105

6381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.394

AC:

59899

AN:

151986

Hom.:

12152

Cov.:

AF XY:

0.401

AC XY:

29787

AN XY:

74270

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1843

3687

5530

7374

9217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

6.7

(source)

DANN

Benign

0.86

PhyloP100

0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over