rs145198292

Variant names:

• chr5-150521327-A-G
• rs145198292
• NM_001543.5:c.73A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-150521327-A-G
• chr5-150521327-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001543.5(NDST1):​c.73A>G​(p.Ile25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,613,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I25F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003347963).
• BP6: Variant 5-150521327-A-G is Benign according to our data. Variant chr5-150521327-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 435940.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001543.5. 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
	NDST1	NM_001543.5	MANE Select	c.73A>G	p.Ile25Val	missense	Exon 2 of 15	NP_001534.1	P52848-1
	NDST1	NM_001301063.2		c.73A>G	p.Ile25Val	missense	Exon 2 of 14	NP_001287992.1	P52848-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDST1	ENST00000261797.7	TSL:1 MANE Select	c.73A>G	p.Ile25Val	missense	Exon 2 of 15	ENSP00000261797.6	P52848-1
	NDST1	ENST00000891672.1		c.73A>G	p.Ile25Val	missense	Exon 2 of 15	ENSP00000561731.1
	NDST1	ENST00000965562.1		c.73A>G	p.Ile25Val	missense	Exon 3 of 16	ENSP00000635621.1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 151856 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00532

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.000480 AC: 120 AN: 250072 AF XY: 0.000392

Gnomad AFR exome AF: 0.00609

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000184 AC: 269 AN: 1461198 Hom.: 1 Cov.: 31 AF XY: 0.000162 AC XY: 118 AN XY: 726972

African (AFR) AF: 0.00574 AC: 192 AN: 33476

American (AMR) AF: 0.000402 AC: 18 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52852

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111920

Other (OTH) AF: 0.000480 AC: 29 AN: 60380

GnomAD4 genome AF: 0.00162 AC: 246 AN: 151972 Hom.: 0 Cov.: 32 AF XY: 0.00148 AC XY: 110 AN XY: 74332

African (AFR) AF: 0.00533 AC: 221 AN: 41440

American (AMR) AF: 0.00118 AC: 18 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67936

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.000716 Hom.: 0

Bravo AF: 0.00179

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000486 AC: 59

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.022
DANN	Benign	0.091
DEOGEN2	Benign	0.17	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.13	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		-0.21
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.048
MVP		0.23
MPC		0.55
ClinPred		0.0033	T
GERP RS		-9.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.016
gMVP		0.20
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145198292; hg19: chr5-149900889;