Genetic Variant ITPRID1:p.Pro40Ser (chr7-31553142-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001257967.3(ITPRID1):c.118C>T(p.Pro40Ser) 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. 13/21 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. P40A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITPRID1
NM_001257967.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.588

Publications

1 publications found

Variant links:

Genes affected

ITPRID1 (HGNC:27363): (ITPR interacting domain containing 1) Predicted to enable signaling receptor binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ITPRID1 links:

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ACMG classification

Classification was made for transcript

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=0.17756951).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRID1	NM_001257967.3	MANE Select	c.118C>T	p.Pro40Ser	missense	Exon 3 of 15	NP_001244896.2	Q6ZRS4-1
ITPRID1	NM_194300.5		c.118C>T	p.Pro40Ser	missense	Exon 2 of 14	NP_919276.2	Q6ZRS4-1
ITPRID1	NM_001257968.3		c.118C>T	p.Pro40Ser	missense	Exon 2 of 15	NP_001244897.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ITPRID1	ENST00000615280.5	TSL:2 MANE Select	c.118C>T	p.Pro40Ser	missense	Exon 3 of 15	ENSP00000478518.2	Q6ZRS4-1
ITPRID1	ENST00000407970.7	TSL:1	c.118C>T	p.Pro40Ser	missense	Exon 2 of 14	ENSP00000384416.3	Q6ZRS4-1
ITPRID1	ENST00000888409.1		c.118C>T	p.Pro40Ser	missense	Exon 2 of 14	ENSP00000558468.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1440162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714048

African (AFR)

AF:

0.00

AC:

AN:

33062

American (AMR)

AF:

0.00

AC:

AN:

42050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25696

East Asian (EAS)

AF:

0.00

AC:

AN:

38670

South Asian (SAS)

AF:

0.00

AC:

AN:

82810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100590

Other (OTH)

AF:

0.00

AC:

AN:

59630

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0045

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.68

M_CAP

Benign

0.010

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.96

PhyloP100

0.59

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.057

Sift

Benign

0.12

Sift4G

Benign

0.13

Polyphen

0.89

Vest4

0.12

MutPred

0.26

Loss of catalytic residue at P40 (P = 0.0019)

MVP

0.32

MPC

0.13

ClinPred

0.62

GERP RS

4.3

Varity_R

0.051

gMVP

0.069

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over