chr9-6328734-C-G

Variant names:

• chr9-6328734-C-G
• rs754731204
• NM_001001874.3:c.139C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001001874.3(TPD52L3):​c.139C>G​(p.Arg47Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R47C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TPD52L3 NM_001001874.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 2 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: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L3	NM_001001874.3	MANE Select	c.139C>G	p.Arg47Gly	missense	Exon 1 of 2	NP_001001874.2	Q96J77-2
	TPD52L3	NM_033516.6		c.139C>G	p.Arg47Gly	missense	Exon 1 of 1	NP_277051.4
	TPD52L3	NM_001001875.4		c.139C>G	p.Arg47Gly	missense	Exon 1 of 2	NP_001001875.2	Q96J77-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPD52L3	ENST00000314556.4	TSL:1 MANE Select	c.139C>G	p.Arg47Gly	missense	Exon 1 of 2	ENSP00000318665.3	Q96J77-2
	TPD52L3	ENST00000381428.1	TSL:1	c.139C>G	p.Arg47Gly	missense	Exon 1 of 2	ENSP00000370836.1	Q96J77-3
	TPD52L3	ENST00000344545.6	TSL:6	c.139C>G	p.Arg47Gly	missense	Exon 1 of 1	ENSP00000341677.5	Q96J77-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	0.071
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		1.2
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.63		Loss of MoRF binding (P = 0.0222)
MVP		0.19
MPC		0.032
ClinPred		0.91	D
GERP RS		3.0
PromoterAI		-0.0084	Neutral
Varity_R		0.86
gMVP		0.28
Mutation Taster		=95/5	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: rs754731204; hg19: chr9-6328734; COSMIC: COSV58827882;