6-125176602-A-C

Variant names:

• chr6-125176602-A-C
• rs4896783
• NM_003287.4:c.19+22632A>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.19+22632A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0486 in 152,306 control chromosomes in the GnomAD database, including 418 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 0.049 (418 hom., cov: 32)
• Consequence: TPD52L1 NM_003287.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L1	NM_003287.4	c.19+22632A>C		intron_variant	Intron 1 of 6	ENST00000534000.6	NP_003278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52L1	ENST00000534000.6	c.19+22632A>C		intron_variant	Intron 1 of 6	1	NM_003287.4	ENSP00000434142.1

Frequencies

GnomAD3 genomes AF: 0.0485 AC: 7388 AN: 152188 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.0576

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0476

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0486 AC: 7398 AN: 152306 Hom.: 418 Cov.: 32 AF XY: 0.0514 AC XY: 3829 AN XY: 74476

African (AFR) AF: 0.0576 AC: 2396 AN: 41562

American (AMR) AF: 0.0409 AC: 626 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1717 AN: 5180

South Asian (SAS) AF: 0.0736 AC: 356 AN: 4834

European-Finnish (FIN) AF: 0.0476 AC: 506 AN: 10622

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0240 AC: 1632 AN: 68018

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0386 Hom.: 77

Bravo AF: 0.0525

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.59
PhyloP100		0.27
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: rs4896783; hg19: chr6-125497748;