Genetic Variant NM_001001874.3:c.352T>C (chr9-6328947-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001001874.3(TPD52L3):c.352T>C(p.Phe118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.946 in 1,614,118 control chromosomes in the GnomAD database, including 723,971 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.92 ( 64315 hom., cov: 31)

Exomes 𝑓: 0.95 ( 659656 hom. )

Consequence

TPD52L3
NM_001001874.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4859298E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L3	NM_001001874.3 link	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2	Q96J77-2A0A140VKH0
TPD52L3	NM_033516.6 link	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 1		NP_277051.4	Q96J77-1
TPD52L3	NM_001001875.4 link	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2		NP_001001875.2	Q96J77-3
TPD52L3	XM_017015280.3 link	c.352T>C	p.Phe118Leu	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.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3	Q96J77-2
TPD52L3	ENST00000381428.1 link	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2	1		ENSP00000370836.1	Q96J77-3
TPD52L3	ENST00000344545.6 link	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 1	6		ENSP00000341677.5	Q96J77-1

Frequencies

GnomAD3 genomes

AF:

0.917

AC:

139434

AN:

152114

Hom.:

64286

Cov.:

show subpopulations

Gnomad AFR

AF:

0.813

Gnomad AMI

AF:

0.954

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.961

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.984

Gnomad MID

AF:

0.921

Gnomad NFE

AF:

0.950

Gnomad OTH

AF:

0.915

GnomAD3 exomes

AF:

0.953

AC:

238962

AN:

250698

Hom.:

114089

AF XY:

0.955

AC XY:

129573

AN XY:

135610

show subpopulations

Gnomad AFR exome

AF:

0.814

Gnomad AMR exome

AF:

0.966

Gnomad ASJ exome

AF:

0.960

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.968

Gnomad FIN exome

AF:

0.982

Gnomad NFE exome

AF:

0.952

Gnomad OTH exome

AF:

0.953

GnomAD4 exome

AF:

0.950

AC:

1388221

AN:

1461886

Hom.:

659656

Cov.:

AF XY:

0.951

AC XY:

691382

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.812

Gnomad4 AMR exome

AF:

0.963

Gnomad4 ASJ exome

AF:

0.961

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.969

Gnomad4 FIN exome

AF:

0.978

Gnomad4 NFE exome

AF:

0.949

Gnomad4 OTH exome

AF:

0.943

GnomAD4 genome

AF:

0.916

AC:

139515

AN:

152232

Hom.:

64315

Cov.:

AF XY:

0.920

AC XY:

68463

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.813

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.961

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.974

Gnomad4 FIN

AF:

0.984

Gnomad4 NFE

AF:

0.950

Gnomad4 OTH

AF:

0.916

Alfa

AF:

0.944

Hom.:

111606

Bravo

AF:

0.910

TwinsUK

AF:

0.945

AC:

3503

ALSPAC

AF:

0.946

AC:

3646

ESP6500AA

AF:

0.825

AC:

3633

ESP6500EA

AF:

0.947

AC:

8142

ExAC

AF:

0.950

AC:

115315

Asia WGS

AF:

0.977

AC:

3397

AN:

3478

EpiCase

AF:

0.945

EpiControl

AF:

0.950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.66

T;T;T

MetaRNN

Benign

0.0000015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

M;M;M

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.7

D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.029

D;D;D

Sift4G

Uncertain

0.050

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.19

MutPred

0.86

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MPC

0.024

ClinPred

0.057

GERP RS

4.4

Varity_R

0.74

gMVP

0.068

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over