9-6328639-C-T

Variant names:

• chr9-6328639-C-T
• rs750791419
• NM_001001874.3:c.44C>T

Variant summary

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

The NM_001001874.3(TPD52L3):​c.44C>T​(p.Ser15Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

Genes affected

TPD52L3 (HGNC:23382): (TPD52 like 3) This gene encodes a member of the tumor protein D52-like family of proteins. These proteins are characterized by an N-terminal coiled-coil motif that is used to form homo- and heteromeric complexes with other tumor protein D52-like proteins. The encoded protein may play a role in spermatogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

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=0.07141444).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L3	NM_001001874.3	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2
TPD52L3	NM_033516.6	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 1		NP_277051.4
TPD52L3	NM_001001875.4	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 2		NP_001001875.2
TPD52L3	XM_017015280.3	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 3		XP_016870769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPD52L3	ENST00000314556.4	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3
TPD52L3	ENST00000381428.1	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 2	1		ENSP00000370836.1
TPD52L3	ENST00000344545.6	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 1	6		ENSP00000341677.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251342 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135848

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461802 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727212

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44C>T (p.S15F) alteration is located in exon 1 (coding exon 1) of the TPD52L3 gene. This alteration results from a C to T substitution at nucleotide position 44, causing the serine (S) at amino acid position 15 to be replaced by a phenylalanine (F). 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	0.13
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.94
DEOGEN2	Benign	0.011	T;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.071	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.045	D;T;D
Sift4G	Uncertain	0.037	D;D;D
Polyphen		0.013	B;B;B
Vest4		0.10
MutPred		0.47		Gain of catalytic residue at S15 (P = 0.0067);Gain of catalytic residue at S15 (P = 0.0067);Gain of catalytic residue at S15 (P = 0.0067);
MVP		0.072
MPC		0.0076
ClinPred		0.12	T
GERP RS		2.6
Varity_R		0.14
gMVP		0.10

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: rs750791419; hg19: chr9-6328639;