9-69723489-G-A

Position:

• chr9-69723489-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099666.2(PTAR1):​c.784C>T​(p.Pro262Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTAR1 NM_001099666.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.657

Genes affected

PTAR1 (HGNC:30449): (protein prenyltransferase alpha subunit repeat containing 1) Predicted to enable protein prenyltransferase activity. Predicted to be involved in protein prenylation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03254339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTAR1	NM_001099666.2	c.784C>T	p.Pro262Ser	missense_variant	6/8	ENST00000340434.5	NP_001093136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTAR1	ENST00000340434.5	c.784C>T	p.Pro262Ser	missense_variant	6/8	1	NM_001099666.2	ENSP00000344299	P1
PTAR1	ENST00000377200.9	c.547C>T	p.Pro183Ser	missense_variant	4/5	1		ENSP00000366405
PTAR1	ENST00000415701.6	c.85C>T	p.Pro29Ser	missense_variant	1/3	3		ENSP00000405943

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.784C>T (p.P262S) alteration is located in exon 6 (coding exon 6) of the PTAR1 gene. This alteration results from a C to T substitution at nucleotide position 784, causing the proline (P) at amino acid position 262 to be replaced by a serine (S). 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	0.069
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.0
DANN	Benign	0.39
DEOGEN2	Benign	0.0041	.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.033	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.51	N;N
REVEL	Benign	0.024
Sift	Benign	0.76	T;T
Sift4G	Benign	0.86	T;T
Polyphen		0.0	.;B
Vest4		0.039
MutPred		0.18		.;Gain of helix (P = 0.0117);
MVP		0.043
MPC		0.31
ClinPred		0.025	T
GERP RS		-3.5
Varity_R		0.033
gMVP		0.14

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: chr9-72338405; COSMIC: COSV100466352;