3-189238845-C-A

Variant names:

• chr3-189238845-C-A
• NM_198485.4:c.415C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198485.4(TPRG1):​c.415C>A​(p.Pro139Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPRG1 NM_198485.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.38

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRG1	NM_198485.4	c.415C>A	p.Pro139Thr	missense_variant	Exon 4 of 6	ENST00000345063.8	NP_940887.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPRG1	ENST00000345063.8	c.415C>A	p.Pro139Thr	missense_variant	Exon 4 of 6	1	NM_198485.4	ENSP00000341031.3
TPRG1	ENST00000433971.5	c.415C>A	p.Pro139Thr	missense_variant	Exon 9 of 11	2		ENSP00000412547.1
TPRG1	ENST00000425670.1	c.196C>A	p.Pro66Thr	missense_variant	Exon 2 of 4	3		ENSP00000400171.1
TPRG1-AS2	ENST00000425454.1	n.320G>T		non_coding_transcript_exon_variant	Exon 3 of 3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.415C>A (p.P139T) alteration is located in exon 4 (coding exon 3) of the TPRG1 gene. This alteration results from a C to A substitution at nucleotide position 415, causing the proline (P) at amino acid position 139 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.57	.;T
M_CAP	Benign	0.0094	T
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.28
Sift	Benign	0.058	T;T
Sift4G	Uncertain	0.041	D;D
Polyphen		1.0	D;D
Vest4		0.68
MutPred		0.55		Gain of MoRF binding (P = 0.0799);Gain of MoRF binding (P = 0.0799);
MVP		0.099
MPC		0.20
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.22
gMVP		0.69

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-188956634;