5-174107345-C-G

Variant names:

• chr5-174107345-C-G
• NM_015980.5:c.356C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015980.5(NSG2):​c.356C>G​(p.Ala119Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,434,900 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NSG2 NM_015980.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015980.5. 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
	NSG2	NM_015980.5	MANE Select	c.356C>G	p.Ala119Gly	missense	Exon 5 of 5	NP_057064.1	Q9Y328

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NSG2	ENST00000303177.8	TSL:1 MANE Select	c.356C>G	p.Ala119Gly	missense	Exon 5 of 5	ENSP00000307722.3	Q9Y328
	NSG2	ENST00000519717.1	TSL:1	c.356C>G	p.Ala119Gly	missense	Exon 4 of 4	ENSP00000431119.1	Q9Y328
	NSG2	ENST00000892999.1		c.356C>G	p.Ala119Gly	missense	Exon 5 of 5	ENSP00000563058.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434900 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 708922

African (AFR) AF: 0.00 AC: 0 AN: 32804

American (AMR) AF: 0.00 AC: 0 AN: 42800

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 39042

South Asian (SAS) AF: 0.00 AC: 0 AN: 84004

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5658

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1093474

Other (OTH) AF: 0.00 AC: 0 AN: 59036

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.1	L
PhyloP100		5.7
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.43
Sift	Benign	0.55	T
Sift4G	Benign	0.52	T
Polyphen		0.99	D
Vest4		0.51
MutPred		0.47		Loss of helix (P = 0.0558)
MVP		0.31
MPC		0.39
ClinPred		0.86	D
GERP RS		5.1
Varity_R		0.31
gMVP		0.69
Mutation Taster		=34/66	disease causing

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

Other links and lift over

hg19: chr5-173534348;