NM_001001874.3:c.278A>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 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.278A>G	p.Lys93Arg	missense	Exon 1 of 2	NP_001001874.2	Q96J77-2
	TPD52L3	NM_033516.6		c.278A>G	p.Lys93Arg	missense	Exon 1 of 1	NP_277051.4
	TPD52L3	NM_001001875.4		c.278A>G	p.Lys93Arg	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.278A>G	p.Lys93Arg	missense	Exon 1 of 2	ENSP00000318665.3	Q96J77-2
	TPD52L3	ENST00000381428.1	TSL:1	c.278A>G	p.Lys93Arg	missense	Exon 1 of 2	ENSP00000370836.1	Q96J77-3
	TPD52L3	ENST00000344545.6	TSL:6	c.278A>G	p.Lys93Arg	missense	Exon 1 of 1	ENSP00000341677.5	Q96J77-1

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

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: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112010

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

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.034	D
Polyphen		0.96	D
Vest4		0.17
MutPred		0.83		Loss of ubiquitination at K93 (P = 0.0496)
MVP		0.088
MPC		0.037
ClinPred		0.98	D
GERP RS		4.4
PromoterAI		-0.022	Neutral
Varity_R		0.26
gMVP		0.059
Mutation Taster		=85/15	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

hg19: chr9-6328873; COSMIC: COSV58828955;