chr9-104768977-C-T

Variant names:

• chr9-104768977-C-T
• NM_018376.4:c.386C>T

Variant summary

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

The NM_018376.4(NIPSNAP3B):​c.386C>T​(p.Thr129Ile) 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 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: 32)
• Consequence: NIPSNAP3B NM_018376.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.295
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08662787).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3B	NM_018376.4	c.386C>T	p.Thr129Ile	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.386C>T	p.Thr129Ile	missense_variant	Exon 3 of 6	1	NM_018376.4	ENSP00000363894.3
NIPSNAP3B	ENST00000460936.5	n.386C>T		non_coding_transcript_exon_variant	Exon 3 of 6	5		ENSP00000435209.1
NIPSNAP3B	ENST00000461177.1	n.221C>T		non_coding_transcript_exon_variant	Exon 2 of 6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.386C>T (p.T129I) alteration is located in exon 3 (coding exon 3) of the NIPSNAP3B gene. This alteration results from a C to T substitution at nucleotide position 386, causing the threonine (T) at amino acid position 129 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.29
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.082
Sift	Benign	0.12	T
Sift4G	Uncertain	0.039	D
Polyphen		0.031	B
Vest4		0.075
MutPred		0.54		Gain of sheet (P = 0.0149);
MVP		0.39
MPC		0.038
ClinPred		0.18	T
GERP RS		0.65
Varity_R		0.14
gMVP		0.51
Mutation Taster		=92/8	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

hg19: chr9-107531258; COSMIC: COSV104688346;