9-6328707-A-G

Variant names:

• chr9-6328707-A-G
• NM_001001874.3:c.112A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001874.3(TPD52L3):​c.112A>G​(p.Lys38Glu) 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 benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14657578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPD52L3	NM_001001874.3	c.112A>G	p.Lys38Glu	missense_variant	Exon 1 of 2	ENST00000314556.4	NP_001001874.2
TPD52L3	NM_033516.6	c.112A>G	p.Lys38Glu	missense_variant	Exon 1 of 1		NP_277051.4
TPD52L3	NM_001001875.4	c.112A>G	p.Lys38Glu	missense_variant	Exon 1 of 2		NP_001001875.2
TPD52L3	XM_017015280.3	c.112A>G	p.Lys38Glu	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.112A>G	p.Lys38Glu	missense_variant	Exon 1 of 2	1	NM_001001874.3	ENSP00000318665.3
TPD52L3	ENST00000381428.1	c.112A>G	p.Lys38Glu	missense_variant	Exon 1 of 2	1		ENSP00000370836.1
TPD52L3	ENST00000344545.6	c.112A>G	p.Lys38Glu	missense_variant	Exon 1 of 1	6		ENSP00000341677.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.112A>G (p.K38E) 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 112, causing the lysine (K) at amino acid position 38 to be replaced by a glutamic acid (E). 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	0.095
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.76	T;T;T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D;D;D
REVEL	Benign	0.096
Sift	Benign	0.053	T;T;T
Sift4G	Uncertain	0.044	D;D;D
Polyphen		0.15	B;B;B
Vest4		0.11
MutPred		0.61		Loss of ubiquitination at K38 (P = 0.0077);Loss of ubiquitination at K38 (P = 0.0077);Loss of ubiquitination at K38 (P = 0.0077);
MVP		0.055
MPC		0.0073
ClinPred		0.83	D
GERP RS		2.4
Varity_R		0.48
gMVP		0.23

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: chr9-6328707;