rs606231457

Positions:

• chr5-150542927-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP2 PP3_Moderate PP5

The NM_001543.5(NDST1):​c.1926G>T​(p.Glu642Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.80

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NDST1. . Gene score misZ 2.9238 (greater than the threshold 3.09). Trascript score misZ 4.3135 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive non-syndromic intellectual disability, intellectual disability, autosomal recessive 46.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854
• PP5: Variant 5-150542927-G-T is Pathogenic according to our data. Variant chr5-150542927-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 161410.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150542927-G-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST1	NM_001543.5	c.1926G>T	p.Glu642Asp	missense_variant	10/15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.1926G>T	p.Glu642Asp	missense_variant	10/14		NP_001287992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDST1	ENST00000261797.7	c.1926G>T	p.Glu642Asp	missense_variant	10/15	1	NM_001543.5	ENSP00000261797.6
NDST1	ENST00000523767.5	c.1926G>T	p.Glu642Asp	missense_variant	10/14	2		ENSP00000428604.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability, autosomal recessive 46 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.94	.;D
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.4	.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.77
MutPred		0.55		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.79
MPC		1.6
ClinPred		1.0	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs606231457; hg19: chr5-149922489;