Variant 5-174046859-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015980.5(NSG2):c.104A>T(p.His35Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000263 in 152,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Consequence

NSG2
NM_015980.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NSG2	NM_015980.5 linkuse as main transcript	c.104A>T	p.His35Leu	missense_variant	2/5	ENST00000303177.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NSG2	ENST00000303177.8 linkuse as main transcript	c.104A>T	p.His35Leu	missense_variant	2/5	1	NM_015980.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251418

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.0000967

Gnomad4 AMR

AF:

0.00

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

ExAC

AF:

0.00000824

AC:

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

Jan 26, 2022

The c.104A>T (p.H35L) alteration is located in exon 2 (coding exon 1) of the HMP19 gene. This alteration results from a A to T substitution at nucleotide position 104, causing the histidine (H) at amino acid position 35 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

0.29

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;.;.;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

.;D;T;D

M_CAP

Benign

0.0087

MetaRNN

Uncertain

0.50

D;D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.017

D;D;D;D

Polyphen

0.80

P;.;.;.

Vest4

0.56

MVP

0.36

MPC

0.57

ClinPred

0.96

GERP RS

4.0

Varity_R

0.49

gMVP

0.54

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