5-150553241-G-C

Variant names:

• chr5-150553241-G-C
• NM_001543.5:c.2558G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001543.5(NDST1):​c.2558G>C​(p.Arg853Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.67

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.891

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST1	NM_001543.5	c.2558G>C	p.Arg853Pro	missense_variant	Exon 15 of 15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.2387G>C	p.Arg796Pro	missense_variant	Exon 14 of 14		NP_001287992.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDST1	ENST00000261797.7	c.2558G>C	p.Arg853Pro	missense_variant	Exon 15 of 15	1	NM_001543.5	ENSP00000261797.6
NDST1	ENST00000523767.5	c.2387G>C	p.Arg796Pro	missense_variant	Exon 14 of 14	2		ENSP00000428604.1
NDST1	ENST00000521752.1	n.99G>C		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461382 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726996

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.88	.;D
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	0.74	D
MutationAssessor	Pathogenic	3.6	.;H
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.020	D;D
Sift4G	Benign	0.066	T;T
Polyphen		1.0	D;D
Vest4		0.84
MutPred		0.65		.;Loss of catalytic residue at R853 (P = 0.0152);
MVP		0.93
MPC		2.0
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.98
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-149932803;