chr5-150521327-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001543.5(NDST1):​c.73A>T​(p.Ile25Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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: 0.0000014 (0 hom.)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036424518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST1	NM_001543.5	c.73A>T	p.Ile25Phe	missense_variant	Exon 2 of 15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.73A>T	p.Ile25Phe	missense_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.73A>T	p.Ile25Phe	missense_variant	Exon 2 of 15	1	NM_001543.5	ENSP00000261797.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461198 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726972

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	1.4
DANN	Benign	0.61
DEOGEN2	Benign	0.26	.;.;.;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.60	T;T;T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.036	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;.;.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.030
Sift	Uncertain	0.017	D;T;T;T
Sift4G	Benign	0.070	T;T;T;T
Polyphen		0.052	.;.;B;B
Vest4		0.20, 0.14
MutPred		0.37		Loss of stability (P = 0.1245);Loss of stability (P = 0.1245);Loss of stability (P = 0.1245);Loss of stability (P = 0.1245);
MVP		0.41
MPC		1.1
ClinPred		0.11	T
GERP RS		-9.9
Varity_R		0.055
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr5-149900889;