9-6328947-T-C

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: š‘“ 0.92 ( 64315 hom., cov: 31)
Exomes š‘“: 0.95 ( 659656 hom. )

Consequence

TPD52L3
NM_001001874.3 missense

Scores

3
7
8

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]

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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
TPD52L3NM_001001874.3 linkc.352T>C p.Phe118Leu missense_variant Exon 1 of 2 ENST00000314556.4 NP_001001874.2 Q96J77-2A0A140VKH0
TPD52L3NM_033516.6 linkc.352T>C p.Phe118Leu missense_variant Exon 1 of 1 NP_277051.4 Q96J77-1
TPD52L3NM_001001875.4 linkc.352T>C p.Phe118Leu missense_variant Exon 1 of 2 NP_001001875.2 Q96J77-3
TPD52L3XM_017015280.3 linkc.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 Appris UniProt
TPD52L3ENST00000314556.4 linkc.352T>C p.Phe118Leu missense_variant Exon 1 of 2 1 NM_001001874.3 ENSP00000318665.3 Q96J77-2
TPD52L3ENST00000381428.1 linkc.352T>C p.Phe118Leu missense_variant Exon 1 of 2 1 ENSP00000370836.1 Q96J77-3
TPD52L3ENST00000344545.6 linkc.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.:
31
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.:
86
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.:
31
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
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.;.
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.66
T;T;T
MetaRNN
Benign
0.0000015
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.2
M;M;M
PrimateAI
Uncertain
0.56
T
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
T
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.

Other links and lift over

dbSNP: rs3847262; hg19: chr9-6328947; API