9-69732257-C-A

Variant names:

• chr9-69732257-C-A
• rs778437482
• NM_001099666.2:c.524G>T

Variant summary

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

The NM_001099666.2(PTAR1):​c.524G>T​(p.Arg175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,516 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R175Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTAR1 NM_001099666.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• Publications: 0 publications found

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

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=0.16439652).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099666.2. 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
	PTAR1	NM_001099666.2	MANE Select	c.524G>T	p.Arg175Leu	missense	Exon 5 of 8	NP_001093136.1	Q7Z6K3
	PTAR1	NM_001366936.1		c.524G>T	p.Arg175Leu	missense	Exon 5 of 7	NP_001353865.1
	PTAR1	NM_001366937.1		c.524G>T	p.Arg175Leu	missense	Exon 5 of 8	NP_001353866.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTAR1	ENST00000340434.5	TSL:1 MANE Select	c.524G>T	p.Arg175Leu	missense	Exon 5 of 8	ENSP00000344299.4	Q7Z6K3
	PTAR1	ENST00000377200.9	TSL:1	c.287G>T	p.Arg96Leu	missense	Exon 3 of 5	ENSP00000366405.5	X6R9N0
	PTAR1	ENST00000912951.1		c.287G>T	p.Arg96Leu	missense	Exon 3 of 6	ENSP00000583010.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461516 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727054

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44714

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111736

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.084
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.091
Sift	Benign	0.060	T
Sift4G	Uncertain	0.047	D
Polyphen		0.18	B
Vest4		0.45
MutPred		0.47		Loss of solvent accessibility (P = 0.0249)
MVP		0.068
MPC		0.40
ClinPred		0.68	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.40
Mutation Taster		=59/41	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: rs778437482; hg19: chr9-72347173;