9-6328947-T-C

Variant names:

• chr9-6328947-T-C
• rs3847262
• NM_001001874.3:c.352T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55

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 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	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2
TPD52L3	NM_033516.6	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 1		NP_277051.4
TPD52L3	NM_001001875.4	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2		NP_001001875.2
TPD52L3	XM_017015280.3	c.352T>C	p.Phe118Leu	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.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3
TPD52L3	ENST00000381428.1	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 2	1		ENSP00000370836.1
TPD52L3	ENST00000344545.6	c.352T>C	p.Phe118Leu	missense_variant	Exon 1 of 1	6		ENSP00000341677.5

Frequencies

GnomAD3 genomes AF: 0.917 AC: 139434 AN: 152114 Hom.: 64286 Cov.: 31

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

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

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

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

Other links and lift over

dbSNP: rs3847262; hg19: chr9-6328947;