5-150521240-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001543.5(NDST1):c.-15G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,601,446 control chromosomes in the GnomAD database, including 1,254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (249 hom., cov: 32)
  • Exomes 𝑓: 0.011 (1005 hom.)
• Consequence: NDST1 NM_001543.5 5_prime_UTR
• Scores: Splicing: ADA: 0.001033
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.486

Genes affected

NDST1 (HGNC:7680): (N-deacetylase and N-sulfotransferase 1) This gene encodes a member of the heparan sulfate/heparin GlcNAc N-deacetylase/ N-sulfotransferase family. The encoded enzyme is a type II transmembrane protein that resides in the Golgi apparatus. The encoded protein catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to nitrogen of glucosamine in heparan sulfate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-150521240-G-T is Benign according to our data. Variant chr5-150521240-G-T is described in ClinVar as [Benign]. Clinvar id is 1226934.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDST1	NM_001543.5	c.-15G>T		5_prime_UTR_variant	2/15	ENST00000261797.7
NDST1	NM_001301063.2	c.-15G>T		5_prime_UTR_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDST1	ENST00000261797.7	c.-15G>T		5_prime_UTR_variant	2/15	1	NM_001543.5	P1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5275 AN: 152064 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0830

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00995

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.0268

GnomAD3 exomes AF: 0.0245 AC: 5959 AN: 242916 Hom.: 316 AF XY: 0.0220 AC XY: 2905 AN XY: 132116

Gnomad AFR exome AF: 0.0872

Gnomad AMR exome AF: 0.00465

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.00963

Gnomad FIN exome AF: 0.0537

Gnomad NFE exome AF: 0.00250

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0113 AC: 16361 AN: 1449266 Hom.: 1005 Cov.: 31 AF XY: 0.0109 AC XY: 7868 AN XY: 720392

Gnomad4 AFR exome AF: 0.0862

Gnomad4 AMR exome AF: 0.00509

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.00953

Gnomad4 FIN exome AF: 0.0562

Gnomad4 NFE exome AF: 0.000924

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0348 AC: 5302 AN: 152180 Hom.: 249 Cov.: 32 AF XY: 0.0363 AC XY: 2698 AN XY: 74388

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.00993

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0530

Gnomad4 NFE AF: 0.00250

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0154 Hom.: 24

Bravo AF: 0.0355

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	13
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0010
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs3733935; hg19: chr5-149900802; COSMIC: COSV55787429; COSMIC: COSV55787429;