16-19115099-C-G

Variant names:

• chr16-19115099-C-G
• NM_001034841.4:c.638C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001034841.4(ITPRIPL2):​c.638C>G​(p.Ala213Gly) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITPRIPL2 NM_001034841.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.826

Genes affected

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

ENSG00000261427 (HGNC:):

ACMG classification

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=0.11853713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITPRIPL2	NM_001034841.4	c.638C>G	p.Ala213Gly	missense_variant	Exon 1 of 1	ENST00000381440.5	NP_001030013.1
ITPRIPL2	NR_028028.2	n.620C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITPRIPL2	ENST00000381440.5	c.638C>G	p.Ala213Gly	missense_variant	Exon 1 of 1	6	NM_001034841.4	ENSP00000370849.3
ITPRIPL2	ENST00000566735.1	n.652C>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
ENSG00000261427	ENST00000564808.6	n.418+164C>G		intron_variant	Intron 2 of 5	4
ENSG00000261427	ENST00000568526.1	n.211+314C>G		intron_variant	Intron 2 of 4	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.638C>G (p.A213G) alteration is located in exon 1 (coding exon 1) of the ITPRIPL2 gene. This alteration results from a C to G substitution at nucleotide position 638, causing the alanine (A) at amino acid position 213 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.041
Sift	Benign	0.26	T
Sift4G	Uncertain	0.043	D
Polyphen		0.82	P
Vest4		0.16
MutPred		0.29		Loss of sheet (P = 0.0817);
MVP		0.17
ClinPred		0.53	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.64

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-19126421;