5-174221435-T-C

Variant names:

• chr5-174221435-T-C
• rs10475598
• ENST00000521585.5:c.*18+16131T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000521585.5(NSG2):​c.*18+16131T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 151,960 control chromosomes in the GnomAD database, including 19,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (19781 hom., cov: 31)
• Consequence: NSG2 ENST00000521585.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NSG2	ENST00000521585.5	c.*18+16131T>C		intron_variant	Intron 4 of 4	4		ENSP00000429863.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72168 AN: 151844 Hom.: 19736 Cov.: 31

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.451

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.476 AC: 72269 AN: 151960 Hom.: 19781 Cov.: 31 AF XY: 0.475 AC XY: 35274 AN XY: 74302

African (AFR) AF: 0.741 AC: 30707 AN: 41454

American (AMR) AF: 0.473 AC: 7220 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3464

East Asian (EAS) AF: 0.759 AC: 3923 AN: 5166

South Asian (SAS) AF: 0.440 AC: 2115 AN: 4808

European-Finnish (FIN) AF: 0.292 AC: 3081 AN: 10566

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.338 AC: 22942 AN: 67920

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.386 Hom.: 57761

Bravo AF: 0.504

Asia WGS AF: 0.616 AC: 2138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10475598; hg19: chr5-173648438;