17-10829555-A-G

Variant names:

• chr17-10829555-A-G
• rs9903961
• NM_001101387.2:c.-138-3772T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101387.2(PIRT):​c.-138-3772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,206 control chromosomes in the GnomAD database, including 61,757 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61757 hom., cov: 31)
• Consequence: PIRT NM_001101387.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 4 publications found

Genes affected

PIRT (HGNC:37239): (phosphoinositide interacting regulator of transient receptor potential channels) Predicted to enable phosphatidylinositol bisphosphate binding activity and transmembrane transporter binding activity. Predicted to be involved in phosphatidylinositol-mediated signaling and positive regulation of cation channel activity. Predicted to act upstream of or within behavioral response to pain and response to heat. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284876 (HGNC:):

TMEM220-AS1 (HGNC:44357): (TMEM220 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIRT	NM_001101387.2	c.-138-3772T>C		intron_variant	Intron 1 of 1	ENST00000580256.3	NP_001094857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIRT	ENST00000580256.3	c.-138-3772T>C		intron_variant	Intron 1 of 1	2	NM_001101387.2	ENSP00000462046.1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136844 AN: 152088 Hom.: 61691 Cov.: 31

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.842

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.900

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.900 AC: 136970 AN: 152206 Hom.: 61757 Cov.: 31 AF XY: 0.902 AC XY: 67105 AN XY: 74424

African (AFR) AF: 0.873 AC: 36267 AN: 41536

American (AMR) AF: 0.935 AC: 14306 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.933 AC: 3241 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5160 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4042 AN: 4808

European-Finnish (FIN) AF: 0.916 AC: 9723 AN: 10612

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61310 AN: 68002

Other (OTH) AF: 0.901 AC: 1895 AN: 2104

Alfa AF: 0.904 Hom.: 75823

Bravo AF: 0.904

Asia WGS AF: 0.920 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9903961; hg19: chr17-10732872;