9-69723396-C-T

Position:

• chr9-69723396-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001099666.2(PTAR1):​c.877G>A​(p.Glu293Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTAR1 NM_001099666.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2023176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTAR1	NM_001099666.2	c.877G>A	p.Glu293Lys	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.877G>A	p.Glu293Lys	missense_variant	6/8	1	NM_001099666.2	ENSP00000344299	P1
PTAR1	ENST00000377200.9	c.640G>A	p.Glu214Lys	missense_variant	4/5	1		ENSP00000366405
PTAR1	ENST00000415701.6	c.178G>A	p.Glu60Lys	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 27, 2023

The c.877G>A (p.E293K) alteration is located in exon 6 (coding exon 6) of the PTAR1 gene. This alteration results from a G to A substitution at nucleotide position 877, causing the glutamic acid (E) at amino acid position 293 to be replaced by a lysine (K). 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	0.087
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.010	.;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.11
Sift	Benign	0.35	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.0030	.;B
Vest4		0.32
MutPred		0.51		.;Gain of methylation at E293 (P = 0.0189);
MVP		0.15
MPC		0.35
ClinPred		0.32	T
GERP RS		6.0
Varity_R		0.18
gMVP		0.24

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: chr9-72338312;