rs1370295552

Variant names:

• chr1-45714457-T-A
• NM_005897.3:c.1319A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-45714457-T-A
• chr1-45714457-T-C
• chr1-45714457-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005897.3(IPP):​c.1319A>T​(p.Tyr440Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. Y440C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IPP NM_005897.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.06

Genes affected

IPP (HGNC:6108): (intracisternal A particle-promoted polypeptide) The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 50 amino acid repeat which interacts with actin. Transcript variants have been described but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IPP	NM_005897.3	c.1319A>T	p.Tyr440Phe	missense_variant	Exon 8 of 9	ENST00000396478.4	NP_005888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IPP	ENST00000396478.4	c.1319A>T	p.Tyr440Phe	missense_variant	Exon 8 of 9	2	NM_005897.3	ENSP00000379739.3
IPP	ENST00000359942.8	c.1319A>T	p.Tyr440Phe	missense_variant	Exon 8 of 10	1		ENSP00000353024.4
IPP	ENST00000495072.1	n.-205A>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	.;D
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Pathogenic	0.84
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		1.0	.;D
Vest4		0.62
MutPred		0.82		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.79
MPC		0.61
ClinPred		0.98	D
GERP RS		4.9
Varity_R		0.57
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-46180129;