5-150521240-G-T

Variant names:

• chr5-150521240-G-T
• rs3733935
• NM_001543.5:c.-15G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

NDST1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 46

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NDST1	NM_001543.5	c.-15G>T		5_prime_UTR_variant	Exon 2 of 15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.-15G>T		5_prime_UTR_variant	Exon 2 of 14		NP_001287992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDST1	ENST00000261797.7	c.-15G>T		5_prime_UTR_variant	Exon 2 of 15	1	NM_001543.5	ENSP00000261797.6

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

GnomAD2 exomes AF: 0.0245 AC: 5959 AN: 242916 AF XY: 0.0220

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 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

African (AFR) AF: 0.0862 AC: 2874 AN: 33340

American (AMR) AF: 0.00509 AC: 227 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 323 AN: 26058

East Asian (EAS) AF: 0.188 AC: 7442 AN: 39552

South Asian (SAS) AF: 0.00953 AC: 821 AN: 86160

European-Finnish (FIN) AF: 0.0562 AC: 2557 AN: 45516

Middle Eastern (MID) AF: 0.00400 AC: 23 AN: 5754

European-Non Finnish (NFE) AF: 0.000924 AC: 1024 AN: 1108244

Other (OTH) AF: 0.0178 AC: 1070 AN: 60066

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

African (AFR) AF: 0.0832 AC: 3458 AN: 41562

American (AMR) AF: 0.00993 AC: 152 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.153 AC: 782 AN: 5114

South Asian (SAS) AF: 0.0151 AC: 73 AN: 4828

European-Finnish (FIN) AF: 0.0530 AC: 563 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00250 AC: 170 AN: 67970

Other (OTH) AF: 0.0327 AC: 69 AN: 2112

Alfa AF: 0.0149 Hom.: 27

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

Jun 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.77
PhyloP100		0.49
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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