5-150521294-G-C

Variant names:

• chr5-150521294-G-C
• NM_001543.5:c.40G>C

Variant summary

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

The NM_001543.5(NDST1):​c.40G>C​(p.Val14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,112 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: 6.8e-7 (0 hom.)
• Consequence: NDST1 NM_001543.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=0.04249367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDST1	NM_001543.5	c.40G>C	p.Val14Leu	missense_variant	Exon 2 of 15	ENST00000261797.7	NP_001534.1
NDST1	NM_001301063.2	c.40G>C	p.Val14Leu	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.40G>C	p.Val14Leu	missense_variant	Exon 2 of 15	1	NM_001543.5	ENSP00000261797.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460112 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726480

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: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.51
DEOGEN2	Benign	0.15	.;.;.;.;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.76	T;T;T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.042	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.5	.;.;.;.;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.010	N;N;N;N;N
REVEL	Benign	0.068
Sift	Benign	0.47	T;T;T;.;T
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.0	.;.;B;.;B
Vest4		0.071, 0.057
MutPred		0.30		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.19
MPC		0.65
ClinPred		0.066	T
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.021
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr5-149900856;