15-75640096-C-G

Variant names:

• chr15-75640096-C-G
• rs201536781
• NM_018285.4:c.73G>C

Variant summary

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

The NM_018285.4(IMP3):​c.73G>C​(p.Asp25His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D25Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: IMP3 NM_018285.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

Genes affected

IMP3 (HGNC:14497): (IMP U3 small nucleolar ribonucleoprotein 3) This gene encodes the human homolog of the yeast Imp3 protein. The protein localizes to the nucleoli and interacts with the U3 snoRNP complex. The protein contains an S4 domain. [provided by RefSeq, Jul 2008]

ENSG00000275454 (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_018285.4. 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
	IMP3	NM_018285.4	MANE Select	c.73G>C	p.Asp25His	missense	Exon 1 of 1	NP_060755.1	Q9NV31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IMP3	ENST00000403490.3	TSL:6 MANE Select	c.73G>C	p.Asp25His	missense	Exon 1 of 1	ENSP00000385217.1	Q9NV31
	IMP3	ENST00000314852.2	TSL:2	c.73G>C	p.Asp25His	missense	Exon 2 of 2	ENSP00000326981.2	Q9NV31
	ENSG00000275454	ENST00000621523.1	TSL:6	n.337C>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.25	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		3.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.0	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.53
MutPred		0.45		Gain of MoRF binding (P = 0.0534)
MVP		0.68
MPC		1.5
ClinPred		1.0	D
GERP RS		5.1
PromoterAI		-0.017	Neutral
Varity_R		0.89
gMVP		0.47
Mutation Taster		=53/47	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: rs201536781; hg19: chr15-75932437;