NM_198485.4:c.434G>C

Variant names:

• chr3-189238864-G-C
• rs770642820
• NM_198485.4:c.434G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198485.4(TPRG1):​c.434G>C​(p.Arg145Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TPRG1 NM_198485.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• Publications: 2 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]

TPRG1-AS2 (HGNC:41062): (TPRG1 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31712365).

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.434G>C	p.Arg145Pro	missense	Exon 4 of 6	NP_940887.1	Q6ZUI0
	TPRG1-AS2	NR_046722.1		n.301C>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRG1	ENST00000345063.8	TSL:1 MANE Select	c.434G>C	p.Arg145Pro	missense	Exon 4 of 6	ENSP00000341031.3	Q6ZUI0
	TPRG1	ENST00000433971.5	TSL:2	c.434G>C	p.Arg145Pro	missense	Exon 9 of 11	ENSP00000412547.1	Q6ZUI0
	TPRG1	ENST00000867713.1		c.434G>C	p.Arg145Pro	missense	Exon 9 of 11	ENSP00000537772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461200 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726898

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000900 AC: 10 AN: 1111590

Other (OTH) AF: 0.0000166 AC: 1 AN: 60356

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.15
Sift	Benign	0.043	D
Sift4G	Benign	0.071	T
Polyphen		0.0080	B
Vest4		0.64
MutPred		0.52		Gain of ubiquitination at K150 (P = 0.0467)
MVP		0.072
MPC		0.040
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.60
gMVP		0.94
Mutation Taster		=75/25	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: rs770642820; hg19: chr3-188956653;