Variant chr4-114829846-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022569.3(NDST4):c.2443A>G(p.Lys815Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,612,162 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

NDST4
NM_022569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

NDST4 (HGNC:20779): (N-deacetylase and N-sulfotransferase 4) Predicted to enable [heparan sulfate]-glucosamine N-sulfotransferase activity and deacetylase activity. Predicted to be involved in heparan sulfate proteoglycan biosynthetic process, polysaccharide chain biosynthetic process. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

NDST4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NDST4	NM_022569.3 linkuse as main transcript	c.2443A>G	p.Lys815Glu	missense_variant	13/14	ENST00000264363.7
NDST4	XM_017008545.3 linkuse as main transcript	c.1306A>G	p.Lys436Glu	missense_variant	12/13
NDST4	XM_017008546.2 linkuse as main transcript	c.1306A>G	p.Lys436Glu	missense_variant	11/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDST4	ENST00000264363.7 linkuse as main transcript	c.2443A>G	p.Lys815Glu	missense_variant	13/14	1	NM_022569.3	P1	Q9H3R1-1
NDST4	ENST00000504854.1 linkuse as main transcript	c.*294A>G		3_prime_UTR_variant, NMD_transcript_variant	12/13	1			Q9H3R1-2
NDST4	ENST00000613194.4 linkuse as main transcript	c.*294A>G		3_prime_UTR_variant	14/15	5			Q9H3R1-2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000600

AC:

AN:

249976

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000175

AC:

256

AN:

1459982

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

122

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000223

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000112

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 23, 2023

The c.2443A>G (p.K815E) alteration is located in exon 13 (coding exon 12) of the NDST4 gene. This alteration results from a A to G substitution at nucleotide position 2443, causing the lysine (K) at amino acid position 815 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.056

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.53

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.020

Polyphen

0.78

Vest4

0.69

MVP

0.88

MPC

0.35

ClinPred

0.30

GERP RS

5.6

Varity_R

0.65

gMVP

0.56

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over