Variant 4-114833661-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022569.3(NDST4):c.2341G>A(p.Glu781Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000021 ( 0 hom. )

Consequence

NDST4
NM_022569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28743327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST4	NM_022569.3 linkuse as main transcript	c.2341G>A	p.Glu781Lys	missense_variant	12/14	ENST00000264363.7	NP_072091.1	Q9H3R1-1A8K0V5
NDST4	XM_017008545.3 linkuse as main transcript	c.1204G>A	p.Glu402Lys	missense_variant	11/13		XP_016864034.1
NDST4	XM_017008546.2 linkuse as main transcript	c.1204G>A	p.Glu402Lys	missense_variant	10/12		XP_016864035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDST4	ENST00000264363.7 linkuse as main transcript	c.2341G>A	p.Glu781Lys	missense_variant	12/14	1	NM_022569.3	ENSP00000264363.2	Q9H3R1-1
NDST4	ENST00000504854.1 linkuse as main transcript	n.*192G>A		non_coding_transcript_exon_variant	11/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000504854.1 linkuse as main transcript	n.*192G>A		3_prime_UTR_variant	11/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000613194 linkuse as main transcript	c.*192G>A		3_prime_UTR_variant	13/15	5		ENSP00000483949.1	Q9H3R1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461064

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 10, 2024

The c.2341G>A (p.E781K) alteration is located in exon 12 (coding exon 11) of the NDST4 gene. This alteration results from a G to A substitution at nucleotide position 2341, causing the glutamic acid (E) at amino acid position 781 to be replaced by a lysine (K). 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

Benign

0.11

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Benign

-0.16

Eigen_PC

Benign

0.094

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.010

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.24

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.31

REVEL

Benign

0.15

Sift

Benign

0.40

Sift4G

Benign

0.67

Polyphen

0.0020

Vest4

0.31

MutPred

0.59

Gain of methylation at E781 (P = 0.0315);

MVP

0.61

MPC

0.54

ClinPred

0.63

GERP RS

5.8

Varity_R

0.56

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over