Genetic Variant TPD52L3:p.Lys108Arg (chr9-6328918-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001874.3(TPD52L3):c.323A>G(p.Lys108Arg) 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 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TPD52L3
NM_001001874.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

Variant links:

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]

TPD52L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18749362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L3	NM_001001874.3 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2	Q96J77-2A0A140VKH0
TPD52L3	NM_033516.6 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 1		NP_277051.4	Q96J77-1
TPD52L3	NM_001001875.4 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 2		NP_001001875.2	Q96J77-3
TPD52L3	XM_017015280.3 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 3		XP_016870769.1	Q96J77-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TPD52L3	ENST00000314556.4 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3	Q96J77-2
TPD52L3	ENST00000381428.1 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 2	1		ENSP00000370836.1	Q96J77-3
TPD52L3	ENST00000344545.6 link	c.323A>G	p.Lys108Arg	missense_variant	Exon 1 of 1	6		ENSP00000341677.5	Q96J77-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152202

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.323A>G (p.K108R) alteration is located in exon 1 (coding exon 1) of the TPD52L3 gene. This alteration results from a A to G substitution at nucleotide position 323, causing the lysine (K) at amino acid position 108 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;.;.

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.092

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.52

T;T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M;M

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.078

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.33

B;P;B

Vest4

0.057

MutPred

0.74

Loss of methylation at K108 (P = 0.0496);Loss of methylation at K108 (P = 0.0496);Loss of methylation at K108 (P = 0.0496);

MVP

0.048

MPC

0.014

ClinPred

0.37

GERP RS

3.2

Varity_R

0.16

gMVP

0.056

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over