rs3847262

Positions:

• chr9-6328947-T-A
• chr9-6328947-T-C
• chr9-6328947-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001001874.3(TPD52L3):​c.352T>A​(p.Phe118Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F118L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• 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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPD52L3	NM_001001874.3	c.352T>A	p.Phe118Ile	missense_variant	1/2	ENST00000314556.4	NP_001001874.2
TPD52L3	NM_033516.6	c.352T>A	p.Phe118Ile	missense_variant	1/1		NP_277051.4
TPD52L3	NM_001001875.4	c.352T>A	p.Phe118Ile	missense_variant	1/2		NP_001001875.2
TPD52L3	XM_017015280.3	c.352T>A	p.Phe118Ile	missense_variant	1/3		XP_016870769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPD52L3	ENST00000314556.4	c.352T>A	p.Phe118Ile	missense_variant	1/2	1	NM_001001874.3	ENSP00000318665
TPD52L3	ENST00000381428.1	c.352T>A	p.Phe118Ile	missense_variant	1/2	1		ENSP00000370836
TPD52L3	ENST00000344545.6	c.352T>A	p.Phe118Ile	missense_variant	1/1			ENSP00000341677	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 86

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.5	H;H;H
MutationTaster	Benign	0.0022	P;P;P
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.45
MutPred		0.91		Gain of methylation at K113 (P = 0.1316);Gain of methylation at K113 (P = 0.1316);Gain of methylation at K113 (P = 0.1316);
MVP		0.17
MPC		0.032
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.93
gMVP		0.11

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;