Variant chr5-174107483-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015980.5(NSG2):c.494C>T(p.Pro165Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,609,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

NSG2
NM_015980.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

Variant links:

Genes affected

NSG2 (HGNC:24955): (neuronal vesicle trafficking associated 2) Predicted to enable clathrin light chain binding activity. Predicted to be involved in clathrin coat assembly and endosomal transport. Located in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

NSG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0074902177).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSG2	NM_015980.5 linkuse as main transcript	c.494C>T	p.Pro165Leu	missense_variant	5/5	ENST00000303177.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSG2	ENST00000303177.8 linkuse as main transcript	c.494C>T	p.Pro165Leu	missense_variant	5/5	1	NM_015980.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000321

AC:

AN:

246342

Hom.:

AF XY:

0.000291

AC XY:

AN XY:

133796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000811

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000182

AC:

265

AN:

1457394

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

123

AN XY:

724100

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000225

Gnomad4 ASJ exome

AF:

0.00599

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.0000424

Gnomad4 OTH exome

AF:

0.000632

GnomAD4 genome

AF:

0.000164

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000335

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2022

The c.494C>T (p.P165L) alteration is located in exon 5 (coding exon 4) of the HMP19 gene. This alteration results from a C to T substitution at nucleotide position 494, causing the proline (P) at amino acid position 165 to be replaced by a leucine (L). 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

0.076

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.021

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.91

REVEL

Benign

0.092

Sift

Uncertain

0.017

Sift4G

Benign

0.093

Polyphen

0.74

Vest4

0.21

MVP

0.32

MPC

0.63

ClinPred

0.051

GERP RS

5.3

Varity_R

0.18

gMVP

0.61

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