3-189310390-C-T

Variant names:

• chr3-189310390-C-T
• rs755877455
• NM_198485.4:c.484C>T

Variant summary

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

The NM_198485.4(TPRG1):​c.484C>T​(p.Gln162*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,435,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TPRG1 NM_198485.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.87
• Publications: 1 publications found

Genes affected

TPRG1 (HGNC:24759): (tumor protein p63 regulated 1) Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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_198485.4. 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
	TPRG1	NM_198485.4	MANE Select	c.484C>T	p.Gln162*	stop_gained	Exon 5 of 6	NP_940887.1	Q6ZUI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRG1	ENST00000345063.8	TSL:1 MANE Select	c.484C>T	p.Gln162*	stop_gained	Exon 5 of 6	ENSP00000341031.3	Q6ZUI0
	TPRG1	ENST00000433971.5	TSL:2	c.484C>T	p.Gln162*	stop_gained	Exon 10 of 11	ENSP00000412547.1	Q6ZUI0
	TPRG1	ENST00000867713.1		c.484C>T	p.Gln162*	stop_gained	Exon 10 of 11	ENSP00000537772.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000413 AC: 1 AN: 242166 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1435846 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 714052

African (AFR) AF: 0.00 AC: 0 AN: 32736

American (AMR) AF: 0.00 AC: 0 AN: 42448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39330

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1097556

Other (OTH) AF: 0.00 AC: 0 AN: 58986

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Benign	0.65	D
PhyloP100		2.9
Vest4		0.21
ClinPred		1.0	D
GERP RS		5.0
Mutation Taster		=28/172	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs755877455; hg19: chr3-189028179;