9-104752933-G-C

Variant names:

• chr9-104752933-G-C
• rs2274870
• NM_015469.3:c.299G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015469.3(NIPSNAP3A):​c.299G>C​(p.Arg100Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. R100R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NIPSNAP3A NM_015469.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.952
• Publications: 41 publications found

Genes affected

NIPSNAP3A (HGNC:23619): (nipsnap homolog 3A) NIPSNAP3A belongs to a family of proteins with putative roles in vesicular transport (Buechler et al., 2004 [PubMed 15177564]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015469.3. 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
	NIPSNAP3A	NM_015469.3	MANE Select	c.299G>C	p.Arg100Pro	missense	Exon 3 of 6	NP_056284.1	Q9UFN0
	NIPSNAP3A	NM_001329570.2		c.299G>C	p.Arg100Pro	missense	Exon 3 of 5	NP_001316499.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPSNAP3A	ENST00000374767.5	TSL:1 MANE Select	c.299G>C	p.Arg100Pro	missense	Exon 3 of 6	ENSP00000363899.4	Q9UFN0
	NIPSNAP3A	ENST00000939849.1		c.299G>C	p.Arg100Pro	missense	Exon 3 of 6	ENSP00000609908.1
	NIPSNAP3A	ENST00000887913.1		c.224G>C	p.Arg75Pro	missense	Exon 3 of 6	ENSP00000557972.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.054	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	-0.018	T
MutationAssessor	Pathogenic	3.5	M
PhyloP100		0.95
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.73
MutPred		0.57		Loss of MoRF binding (P = 0.0106)
MVP		0.90
MPC		0.67
ClinPred		1.0	D
GERP RS		1.3
Varity_R		0.97
gMVP		0.97
Mutation Taster		=65/35	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: rs2274870; hg19: chr9-107515214;