1-45727786-C-T

Variant names:

• chr1-45727786-C-T
• rs376684550
• NM_005897.3:c.893G>A

Variant summary

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

The NM_005897.3(IPP):​c.893G>A​(p.Arg298Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000453 in 1,545,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R298W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: IPP NM_005897.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87
• 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]

ENSG00000302565 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.893G>A	p.Arg298Gln	missense	Exon 5 of 9	NP_005888.1	Q9Y573-1
	IPP	NM_001145349.2		c.893G>A	p.Arg298Gln	missense	Exon 5 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.893G>A	p.Arg298Gln	missense	Exon 5 of 9	ENSP00000379739.3	Q9Y573-1
	IPP	ENST00000359942.8	TSL:1	c.893G>A	p.Arg298Gln	missense	Exon 5 of 10	ENSP00000353024.4	Q9Y573-2
	IPP	ENST00000890995.1		c.893G>A	p.Arg298Gln	missense	Exon 6 of 10	ENSP00000561054.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000359 AC: 5 AN: 1393448 Hom.: 0 Cov.: 30 AF XY: 0.00000583 AC XY: 4 AN XY: 686200

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.0000701 AC: 3 AN: 42784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24716

East Asian (EAS) AF: 0.00 AC: 0 AN: 38782

South Asian (SAS) AF: 0.00 AC: 0 AN: 75688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5478

European-Non Finnish (NFE) AF: 0.00000188 AC: 2 AN: 1064974

Other (OTH) AF: 0.00 AC: 0 AN: 57068

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151974 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74240

African (AFR) AF: 0.0000242 AC: 1 AN: 41364

American (AMR) AF: 0.0000656 AC: 1 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

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	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.9
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.59
MVP		0.83
MPC		0.20
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.31
gMVP		0.75
Mutation Taster		=78/22	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: rs376684550; hg19: chr1-46193458;