9-6328873-A-G

Variant names:

• chr9-6328873-A-G
• NM_001001874.3:c.278A>G

Variant summary

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

The NM_001001874.3(TPD52L3):​c.278A>G​(p.Lys93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03

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.278A>G	p.Lys93Arg	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2
TPD52L3	NM_033516.6	c.278A>G	p.Lys93Arg	missense_variant	Exon 1 of 1		NP_277051.4
TPD52L3	NM_001001875.4	c.278A>G	p.Lys93Arg	missense_variant	Exon 1 of 2		NP_001001875.2
TPD52L3	XM_017015280.3	c.278A>G	p.Lys93Arg	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.278A>G	p.Lys93Arg	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3
TPD52L3	ENST00000381428.1	c.278A>G	p.Lys93Arg	missense_variant	Exon 1 of 2	1		ENSP00000370836.1
TPD52L3	ENST00000344545.6	c.278A>G	p.Lys93Arg	missense_variant	Exon 1 of 1	6		ENSP00000341677.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461890 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.278A>G (p.K93R) alteration is located in exon 1 (coding exon 1) of the TPD52L3 gene. This alteration results from a A to G substitution at nucleotide position 278, causing the lysine (K) at amino acid position 93 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.079	T;.;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.029	D;D;D
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.96	D;P;P
Vest4		0.17
MutPred		0.83		Loss of ubiquitination at K93 (P = 0.0496);Loss of ubiquitination at K93 (P = 0.0496);Loss of ubiquitination at K93 (P = 0.0496);
MVP		0.088
MPC		0.037
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.26
gMVP		0.059

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-6328873; COSMIC: COSV58828955;