chr9-104768889-C-G

Variant names:

• chr9-104768889-C-G
• rs745675891
• NM_018376.4:c.298C>G

Variant summary

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

The NM_018376.4(NIPSNAP3B):​c.298C>G​(p.Arg100Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,796 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R100Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NIPSNAP3B NM_018376.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

Genes affected

NIPSNAP3B (HGNC:23641): (nipsnap homolog 3B) NIPSNAP3B belongs to a family of proteins with putative roles in vesicular trafficking (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, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3B	NM_018376.4	c.298C>G	p.Arg100Gly	missense_variant	Exon 3 of 6	ENST00000374762.4	NP_060846.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPSNAP3B	ENST00000374762.4	c.298C>G	p.Arg100Gly	missense_variant	Exon 3 of 6	1	NM_018376.4	ENSP00000363894.3
NIPSNAP3B	ENST00000460936.5	n.298C>G		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000435209.1
NIPSNAP3B	ENST00000461177.1	n.133C>G		non_coding_transcript_exon_variant	Exon 2 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454796 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723712

African (AFR) AF: 0.00 AC: 0 AN: 33132

American (AMR) AF: 0.00 AC: 0 AN: 42948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1109018

Other (OTH) AF: 0.00 AC: 0 AN: 60050

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		2.5
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.71
MutPred		0.71		Loss of MoRF binding (P = 0.0279);
MVP		0.78
MPC		0.25
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.93
gMVP		0.94
Mutation Taster		=89/11	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: rs745675891; hg19: chr9-107531170;