rs1415381296

Variant names:

• chr9-6328918-A-C
• rs1415381296
• NM_001001874.3:c.323A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-6328918-A-C
• chr9-6328918-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001874.3(TPD52L3):​c.323A>C​(p.Lys108Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,202 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L3	NM_001001874.3	c.323A>C	p.Lys108Thr	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2
TPD52L3	NM_033516.6	c.323A>C	p.Lys108Thr	missense_variant	Exon 1 of 1		NP_277051.4
TPD52L3	NM_001001875.4	c.323A>C	p.Lys108Thr	missense_variant	Exon 1 of 2		NP_001001875.2
TPD52L3	XM_017015280.3	c.323A>C	p.Lys108Thr	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.323A>C	p.Lys108Thr	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3
TPD52L3	ENST00000381428.1	c.323A>C	p.Lys108Thr	missense_variant	Exon 1 of 2	1		ENSP00000370836.1
TPD52L3	ENST00000344545.6	c.323A>C	p.Lys108Thr	missense_variant	Exon 1 of 1	6		ENSP00000341677.5

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74362

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000478

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.;.
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.2	M;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-5.7	D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.25
MutPred		0.75		Loss of methylation at K108 (P = 0.0281);Loss of methylation at K108 (P = 0.0281);Loss of methylation at K108 (P = 0.0281);
MVP		0.26
MPC		0.036
ClinPred		0.98	D
GERP RS		3.2
Varity_R		0.42
gMVP		0.13

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: rs1415381296; hg19: chr9-6328918;