Genetic Variant NM_018376.4:c.34C>A (chr9-104764274-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018376.4(NIPSNAP3B):c.34C>A(p.Leu12Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,445,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. L12F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NIPSNAP3B
NM_018376.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

0 publications found

Variant links:

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]

NIPSNAP3B links:

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ACMG classification

Classification was made for transcript

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=0.1164549).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP3B	NM_018376.4 link	c.34C>A	p.Leu12Ile	missense_variant	Exon 1 of 6	ENST00000374762.4	NP_060846.2	Q9BS92Q71RE8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NIPSNAP3B	ENST00000374762.4 link	c.34C>A	p.Leu12Ile	missense_variant	Exon 1 of 6	1	NM_018376.4	ENSP00000363894.3	Q9BS92
NIPSNAP3B	ENST00000460936.5 link	n.34C>A		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000435209.1	F2Z3L7
NIPSNAP3B	ENST00000461177.1 link	n.80C>A		non_coding_transcript_exon_variant	Exon 1 of 6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000457

AC:

AN:

218732

AF XY:

0.00000841

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1445004

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33152

American (AMR)

AF:

0.00

AC:

AN:

42506

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25778

East Asian (EAS)

AF:

0.00

AC:

AN:

39006

South Asian (SAS)

AF:

0.00

AC:

AN:

83324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4174

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

1106040

Other (OTH)

AF:

0.00

AC:

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000830

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.039

BayesDel_noAF

Benign

-0.29

CADD

Benign

7.4

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0092

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.74

M_CAP

Benign

0.015

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.4

PhyloP100

-0.11

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.79

REVEL

Benign

0.079

Sift

Benign

0.17

Sift4G

Benign

0.14

Polyphen

0.51

Vest4

0.33

MutPred

0.27

Gain of catalytic residue at L17 (P = 0.0505);

MVP

0.25

MPC

0.035

ClinPred

0.11

GERP RS

1.8

PromoterAI

0.25

Neutral

(source)

Varity_R

0.065

gMVP

0.31

Mutation Taster

=96/4

polymorphism

(source)

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

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NM_018376.4:c.34C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over