3-189207473-C-T

Variant names:

• chr3-189207473-C-T
• rs778674338
• NM_198485.4:c.89C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198485.4(TPRG1):​c.89C>T​(p.Ser30Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: TPRG1 NM_198485.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.57
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15940425).

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.89C>T	p.Ser30Leu	missense	Exon 2 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.89C>T	p.Ser30Leu	missense	Exon 2 of 6	ENSP00000341031.3	Q6ZUI0
	TPRG1	ENST00000433971.5	TSL:2	c.89C>T	p.Ser30Leu	missense	Exon 7 of 11	ENSP00000412547.1	Q6ZUI0
	TPRG1	ENST00000867713.1		c.89C>T	p.Ser30Leu	missense	Exon 7 of 11	ENSP00000537772.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 251316 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: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461798 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727204

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111952

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	0.076
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.43	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.6
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.14
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.025	D
Polyphen		0.98	D
Vest4		0.40
MutPred		0.18		Loss of phosphorylation at S30 (P = 0.007)
MVP		0.072
MPC		0.079
ClinPred		0.75	D
GERP RS		5.8
PromoterAI		-0.015	Neutral
Varity_R		0.13
gMVP		0.39
Mutation Taster		=89/11	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: rs778674338; hg19: chr3-188925262; COSMIC: COSV61465186;