chr9-6328947-T-A

Variant names:

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

Variant summary

Our verdict is Likely pathogenic. The variant received 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 28 publications found

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

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001874.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L3	NM_001001874.3	MANE Select	c.352T>A	p.Phe118Ile	missense	Exon 1 of 2	NP_001001874.2
	TPD52L3	NM_033516.6		c.352T>A	p.Phe118Ile	missense	Exon 1 of 1	NP_277051.4
	TPD52L3	NM_001001875.4		c.352T>A	p.Phe118Ile	missense	Exon 1 of 2	NP_001001875.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L3	ENST00000314556.4	TSL:1 MANE Select	c.352T>A	p.Phe118Ile	missense	Exon 1 of 2	ENSP00000318665.3
	TPD52L3	ENST00000381428.1	TSL:1	c.352T>A	p.Phe118Ile	missense	Exon 1 of 2	ENSP00000370836.1
	TPD52L3	ENST00000344545.6	TSL:6	c.352T>A	p.Phe118Ile	missense	Exon 1 of 1	ENSP00000341677.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 86

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.45
MutPred		0.91		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
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs3847262; hg19: chr9-6328947;