Genetic Variant NM_001483.3:c.46G>C (chr7-55964655-G-C) – 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_001483.3(NIPSNAP2):c.46G>C(p.Gly16Arg) 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. 16/22 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. G16C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NIPSNAP2
NM_001483.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.94

Publications

0 publications found

Variant links:

Genes affected

NIPSNAP2 (HGNC:4179): (nipsnap homolog 2) This gene encodes a member of the NipSnap family of proteins that may be involved in vesicular transport. The encoded protein is localized to mitochondria and plays a role in oxidative phosphorylation. A pseudogene of this gene is located on the long arm of chromosome 2. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]

NIPSNAP2 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=0.15752035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001483.3. 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
	NIPSNAP2	NM_001483.3	MANE Select	c.46G>C	p.Gly16Arg	missense	Exon 1 of 10	NP_001474.1	O75323-1
	NIPSNAP2	NM_001202469.2		c.46G>C	p.Gly16Arg	missense	Exon 1 of 8	NP_001189398.1	O75323-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NIPSNAP2	ENST00000322090.8	TSL:1 MANE Select	c.46G>C	p.Gly16Arg	missense	Exon 1 of 10	ENSP00000313050.3	O75323-1
NIPSNAP2	ENST00000878201.1		c.46G>C	p.Gly16Arg	missense	Exon 1 of 11	ENSP00000548260.1
NIPSNAP2	ENST00000878203.1		c.46G>C	p.Gly16Arg	missense	Exon 1 of 10	ENSP00000548262.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

955882

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

448706

African (AFR)

AF:

0.00

AC:

AN:

18826

American (AMR)

AF:

0.00

AC:

AN:

4558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9146

East Asian (EAS)

AF:

0.00

AC:

AN:

14208

South Asian (SAS)

AF:

0.00

AC:

AN:

18346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840766

Other (OTH)

AF:

0.00

AC:

AN:

34926

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.013

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.63

M_CAP

Benign

0.070

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.090

REVEL

Benign

0.069

Sift

Benign

0.28

Sift4G

Benign

0.38

Polyphen

0.13

Vest4

0.40

MutPred

0.35

Loss of catalytic residue at G16 (P = 0.0079)

MVP

0.54

MPC

0.53

ClinPred

0.21

GERP RS

1.9

PromoterAI

-0.16

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.074

gMVP

0.56

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over