chr1-45716967-C-T

Variant names:

• chr1-45716967-C-T
• rs764461382
• NM_005897.3:c.1237G>A

Variant summary

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

The NM_005897.3(IPP):​c.1237G>A​(p.Asp413Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,010 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IPP NM_005897.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.56
• Publications: 0 publications found

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

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=0.25241604).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005897.3. 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
	IPP	NM_005897.3	MANE Select	c.1237G>A	p.Asp413Asn	missense	Exon 7 of 9	NP_005888.1	Q9Y573-1
	IPP	NM_001145349.2		c.1237G>A	p.Asp413Asn	missense	Exon 7 of 10	NP_001138821.1	Q9Y573-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPP	ENST00000396478.4	TSL:2 MANE Select	c.1237G>A	p.Asp413Asn	missense	Exon 7 of 9	ENSP00000379739.3	Q9Y573-1
	IPP	ENST00000359942.8	TSL:1	c.1237G>A	p.Asp413Asn	missense	Exon 7 of 10	ENSP00000353024.4	Q9Y573-2
	IPP	ENST00000890995.1		c.1237G>A	p.Asp413Asn	missense	Exon 8 of 10	ENSP00000561054.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251212 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461010 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726856

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000757 AC: 3 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111362

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

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	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.0038
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	0.26	N
PhyloP100		5.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.28
Sift	Benign	0.17	T
Sift4G	Benign	0.19	T
Polyphen		0.087	B
Vest4		0.34
MutPred		0.37		Loss of ubiquitination at K416 (P = 0.0615)
MVP		0.77
MPC		0.24
ClinPred		0.19	T
GERP RS		3.8
Varity_R		0.16
gMVP		0.14
Mutation Taster		=85/15	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: rs764461382; hg19: chr1-46182639;