5-174221435-T-C

Position:

• chr5-174221435-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NSG2	ENST00000521585.5	c.*18+16131T>C		intron_variant		4		ENSP00000429863

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

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.454

Alfa AF: 0.365 Hom.: 24390

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10475598; hg19: chr5-173648438;