6-125220143-A-G

Position:

• chr6-125220143-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001003395.3(TPD52L1):​c.-3A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPD52L1 NM_001003395.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18802795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPD52L1	NM_003287.4	c.85A>G	p.Ser29Gly	missense_variant	2/7	ENST00000534000.6	NP_003278.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPD52L1	ENST00000534000.6	c.85A>G	p.Ser29Gly	missense_variant	2/7	1	NM_003287.4	ENSP00000434142.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2024

The c.85A>G (p.S29G) alteration is located in exon 2 (coding exon 2) of the TPD52L1 gene. This alteration results from a A to G substitution at nucleotide position 85, causing the serine (S) at amino acid position 29 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;T;.;.;T;T
Eigen	Benign	0.024
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.79	T;T;T;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;L;L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.20	T;T;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T;T
Polyphen		0.090, 0.12	.;B;B;B;.;.
Vest4		0.16
MutPred		0.36		Loss of phosphorylation at S29 (P = 0.0098);Loss of phosphorylation at S29 (P = 0.0098);Loss of phosphorylation at S29 (P = 0.0098);Loss of phosphorylation at S29 (P = 0.0098);Loss of phosphorylation at S29 (P = 0.0098);Loss of phosphorylation at S29 (P = 0.0098);
MVP		0.22
MPC		0.55
ClinPred		0.63	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.088

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-125541289;