NM_001034841.4:c.374G>A

Variant names:

• chr16-19114835-G-A
• rs1176161099
• NM_001034841.4:c.374G>A

Variant summary

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

The NM_001034841.4(ITPRIPL2):​c.374G>A​(p.Arg125Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 6.9e-7 (0 hom.)
• Consequence: ITPRIPL2 NM_001034841.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.35
• 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: 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=0.10086915).

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.374G>A	p.Arg125Gln	missense	Exon 1 of 1	NP_001030013.1	Q3MIP1
	ITPRIPL2	NR_028028.2		n.356G>A		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITPRIPL2	ENST00000381440.5	TSL:6 MANE Select	c.374G>A	p.Arg125Gln	missense	Exon 1 of 1	ENSP00000370849.3	Q3MIP1
	ENSG00000261427	ENST00000564808.6	TSL:4	n.318G>A		non_coding_transcript_exon	Exon 2 of 6
	ITPRIPL2	ENST00000566735.1	TSL:2	n.388G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1452782 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722160

African (AFR) AF: 0.00 AC: 0 AN: 33234

American (AMR) AF: 0.00 AC: 0 AN: 43502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39184

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108358

Other (OTH) AF: 0.00 AC: 0 AN: 60026

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.46	N
PhyloP100		3.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.059
Sift	Benign	0.38	T
Sift4G	Benign	0.24	T
Polyphen		0.66	P
Vest4		0.082
MutPred		0.41		Loss of MoRF binding (P = 0.0135)
MVP		0.14
ClinPred		0.57	D
GERP RS		3.1
Varity_R		0.036
gMVP		0.66
Mutation Taster		=93/7	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: rs1176161099; hg19: chr16-19126157;