Genetic Variant NIPSNAP2:p.Gly16Cys (chr7-55964655-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001483.3(NIPSNAP2):c.46G>T(p.Gly16Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000208 in 1,105,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

NIPSNAP2
NM_001483.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19879684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPSNAP2	NM_001483.3 link	c.46G>T	p.Gly16Cys	missense_variant	Exon 1 of 10	ENST00000322090.8	NP_001474.1	O75323-1
NIPSNAP2	NM_001202469.2 link	c.46G>T	p.Gly16Cys	missense_variant	Exon 1 of 8		NP_001189398.1	O75323-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPSNAP2	ENST00000322090.8 link	c.46G>T	p.Gly16Cys	missense_variant	Exon 1 of 10	1	NM_001483.3	ENSP00000313050.3		O75323-1

Frequencies

GnomAD3 genomes

AF:

0.000121

AC:

AN:

149260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000665

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000523

AC:

AN:

955882

Hom.:

Cov.:

AF XY:

0.00000223

AC XY:

AN XY:

448706

show subpopulations

Gnomad4 AFR exome

AF:

0.000106

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000545

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000286

GnomAD4 genome

AF:

0.000121

AC:

AN:

149260

Hom.:

Cov.:

AF XY:

0.0000824

AC XY:

AN XY:

72774

show subpopulations

Gnomad4 AFR

AF:

0.000414

Gnomad4 AMR

AF:

0.0000665

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000869

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.46G>T (p.G16C) alteration is located in exon 1 (coding exon 1) of the GBAS gene. This alteration results from a G to T substitution at nucleotide position 46, causing the glycine (G) at amino acid position 16 to be replaced by a cysteine (C). 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

0.14

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.59

T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.13

Sift

Benign

0.032

D;T

Sift4G

Benign

0.10

T;T

Polyphen

0.78

P;.

Vest4

0.35

MutPred

0.40

Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);

MVP

0.60

MPC

0.49

ClinPred

0.30

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.15

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over