16-19114607-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001034841.4(ITPRIPL2):​c.146C>T​(p.Pro49Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000379 in 1,583,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ITPRIPL2
NM_001034841.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27
Variant links:
Genes affected
ITPRIPL2 (HGNC:27257): (ITPRIP like 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18004468).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITPRIPL2NM_001034841.4 linkc.146C>T p.Pro49Leu missense_variant Exon 1 of 1 ENST00000381440.5 NP_001030013.1 Q3MIP1
ITPRIPL2NR_028028.2 linkn.162-34C>T intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITPRIPL2ENST00000381440.5 linkc.146C>T p.Pro49Leu missense_variant Exon 1 of 1 6 NM_001034841.4 ENSP00000370849.3 Q3MIP1
ENSG00000261427ENST00000564808.6 linkn.124-34C>T intron_variant Intron 1 of 5 4
ITPRIPL2ENST00000566735.1 linkn.194-34C>T intron_variant Intron 1 of 1 2
ENSG00000261427ENST00000568526.1 linkn.67-34C>T intron_variant Intron 1 of 4 5

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000431
AC:
9
AN:
208878
Hom.:
0
AF XY:
0.0000525
AC XY:
6
AN XY:
114358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000131
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000386
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000429
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000391
AC:
56
AN:
1431770
Hom.:
0
Cov.:
31
AF XY:
0.0000479
AC XY:
34
AN XY:
710524
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000121
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000488
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000418
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152196
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000427
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000414
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.146C>T (p.P49L) alteration is located in exon 1 (coding exon 1) of the ITPRIPL2 gene. This alteration results from a C to T substitution at nucleotide position 146, causing the proline (P) at amino acid position 49 to be replaced by a leucine (L). 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
0.15
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
19
DANN
Benign
0.97
DEOGEN2
Benign
0.0043
T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.70
T
M_CAP
Benign
0.059
D
MetaRNN
Benign
0.18
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.10
Sift
Benign
0.18
T
Sift4G
Uncertain
0.033
D
Polyphen
0.90
P
Vest4
0.35
MutPred
0.39
Gain of helix (P = 0.0078);
MVP
0.36
ClinPred
0.075
T
GERP RS
3.5
Varity_R
0.076
gMVP
0.41

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766626359; hg19: chr16-19125929; API