9-104753041-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015469.3(NIPSNAP3A):c.407A>T(p.Lys136Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NIPSNAP3A NM_015469.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPSNAP3A	NM_015469.3	c.407A>T	p.Lys136Ile	missense_variant	3/6	ENST00000374767.5
NIPSNAP3A	NM_001329570.2	c.407A>T	p.Lys136Ile	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPSNAP3A	ENST00000374767.5	c.407A>T	p.Lys136Ile	missense_variant	3/6	1	NM_015469.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2023

The c.407A>T (p.K136I) alteration is located in exon 3 (coding exon 3) of the NIPSNAP3A gene. This alteration results from a A to T substitution at nucleotide position 407, causing the lysine (K) at amino acid position 136 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	0.22
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.54	D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.1	M
MutationTaster	Benign	0.94	D
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.94	P
Vest4		0.35
MutPred		0.51		Loss of methylation at K136 (P = 0);
MVP		0.64
MPC		0.56
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.79
gMVP		0.65

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-107515322;