dbSNP rs751035703: NSG1:p.Ala180Glu (chr4-4417416-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014392.5(NSG1):c.539C>A(p.Ala180Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A180V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NSG1
NM_014392.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.81

Publications

0 publications found

Variant links:

Genes affected

NSG1 (HGNC:18790): (neuronal vesicle trafficking associated 1) Predicted to enable clathrin light chain binding activity. Involved in apoptotic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

NSG1 links:

STX18 (HGNC:15942): (syntaxin 18) This gene encodes a member of the syntaxin family of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) which is part of a membrane tethering complex that includes other SNAREs and several peripheral membrane proteins, and is involved in vesicular transport between the endoplasmic reticulum (ER) and the Golgi complex. The encoded protein is important for the organization of the smooth, rough, and exit site ER subdomains. A pseudogene of this gene has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

STX18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NSG1	NM_014392.5	MANE Select	c.539C>A	p.Ala180Glu	missense	Exon 5 of 5	NP_055207.1	P42857-1
NSG1	NM_001382227.1		c.566C>A	p.Ala189Glu	missense	Exon 6 of 6	NP_001369156.1
NSG1	NM_001040101.2		c.539C>A	p.Ala180Glu	missense	Exon 5 of 5	NP_001035190.1	P42857-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NSG1	ENST00000621129.5	TSL:1 MANE Select	c.539C>A	p.Ala180Glu	missense	Exon 5 of 5	ENSP00000480081.1	P42857-1
NSG1	ENST00000513555.5	TSL:1	c.539C>A	p.Ala180Glu	missense	Exon 8 of 8	ENSP00000426358.1	P42857-1
STX18	ENST00000505286.5	TSL:1	c.913-1253G>T		intron	N/A	ENSP00000426648.1	D6RF48

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111990

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0083

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0075

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.5

PhyloP100

6.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.49

REVEL

Uncertain

0.47

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.33

MutPred

0.42

Gain of methylation at K183 (P = 0.1081)

MVP

0.11

MPC

0.67

ClinPred

0.94

GERP RS

4.6

Varity_R

0.27

gMVP

0.66

Mutation Taster

=53/47

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over