NM_001008949.3:c.824G>C

Variant names:

• chr2-96327455-G-C
• rs149860299
• NM_001008949.3:c.824G>C

Variant summary

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

The NM_001008949.3(ITPRIPL1):​c.824G>C​(p.Arg275Pro) 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. 15/22 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. R275C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITPRIPL1 NM_001008949.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 2 publications found

Genes affected

ITPRIPL1 (HGNC:29371): (ITPRIP like 1) Located in membrane. [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=0.20831811).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008949.3. 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
	ITPRIPL1	NM_001008949.3	MANE Select	c.824G>C	p.Arg275Pro	missense	Exon 3 of 3	NP_001008949.1	Q6GPH6-1
	ITPRIPL1	NM_178495.6		c.848G>C	p.Arg283Pro	missense	Exon 1 of 1	NP_848590.3
	ITPRIPL1	NM_001163523.2		c.800G>C	p.Arg267Pro	missense	Exon 2 of 2	NP_001156995.1	Q6GPH6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL1	ENST00000439118.3	TSL:1 MANE Select	c.824G>C	p.Arg275Pro	missense	Exon 3 of 3	ENSP00000389308.2	Q6GPH6-1
	ITPRIPL1	ENST00000420728.1	TSL:2	c.917G>C	p.Arg306Pro	missense	Exon 2 of 2	ENSP00000396552.1	H7C0T2
	ITPRIPL1	ENST00000361124.5	TSL:6	c.848G>C	p.Arg283Pro	missense	Exon 1 of 1	ENSP00000355121.4	Q6GPH6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.54
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.025	D
Polyphen		0.91	P
Vest4		0.51
MutPred		0.39		Loss of ubiquitination at K277 (P = 0.093)
MVP		0.44
MPC		0.27
ClinPred		0.40	T
GERP RS		4.3
Varity_R		0.28
gMVP		0.70
Mutation Taster		=79/21	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: rs149860299; hg19: chr2-96993193;