NM_001034841.4:c.121G>T

Variant names:

• chr16-19114582-G-T
• NM_001034841.4:c.121G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001034841.4(ITPRIPL2):​c.121G>T​(p.Ala41Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ITPRIPL2 NM_001034841.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0500
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04433179).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034841.4. 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
	ITPRIPL2	NM_001034841.4	MANE Select	c.121G>T	p.Ala41Ser	missense	Exon 1 of 1	NP_001030013.1	Q3MIP1
	ITPRIPL2	NR_028028.2		n.162-59G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL2	ENST00000381440.5	TSL:6 MANE Select	c.121G>T	p.Ala41Ser	missense	Exon 1 of 1	ENSP00000370849.3	Q3MIP1
	ENSG00000261427	ENST00000564808.6	TSL:4	n.124-59G>T		intron	N/A
	ITPRIPL2	ENST00000566735.1	TSL:2	n.194-59G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1416914 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 701056

African (AFR) AF: 0.00 AC: 0 AN: 32992

American (AMR) AF: 0.00 AC: 0 AN: 40592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23666

East Asian (EAS) AF: 0.00 AC: 0 AN: 39016

South Asian (SAS) AF: 0.00 AC: 0 AN: 78816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093862

Other (OTH) AF: 0.00 AC: 0 AN: 58736

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.89
DEOGEN2	Benign	0.00062	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.050
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.029
Sift	Benign	0.11	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.028
MutPred		0.13		Gain of disorder (P = 0.0499)
MVP		0.048
ClinPred		0.028	T
GERP RS		1.2
Varity_R		0.048
gMVP		0.11

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

hg19: chr16-19125904;