Variant 4-114839487-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022569.3(NDST4):c.2177C>A(p.Thr726Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Consequence

NDST4
NM_022569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25126997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST4	NM_022569.3 linkuse as main transcript	c.2177C>A	p.Thr726Lys	missense_variant	11/14	ENST00000264363.7	NP_072091.1	Q9H3R1-1A8K0V5
NDST4	XM_017008545.3 linkuse as main transcript	c.1040C>A	p.Thr347Lys	missense_variant	10/13		XP_016864034.1
NDST4	XM_017008546.2 linkuse as main transcript	c.1040C>A	p.Thr347Lys	missense_variant	9/12		XP_016864035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDST4	ENST00000264363.7 linkuse as main transcript	c.2177C>A	p.Thr726Lys	missense_variant	11/14	1	NM_022569.3	ENSP00000264363.2	Q9H3R1-1
NDST4	ENST00000504854.1 linkuse as main transcript	n.*28C>A		non_coding_transcript_exon_variant	10/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000504854.1 linkuse as main transcript	n.*28C>A		3_prime_UTR_variant	10/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000613194 linkuse as main transcript	c.*28C>A		3_prime_UTR_variant	12/15	5		ENSP00000483949.1	Q9H3R1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251380

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

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

Oct 20, 2024

The c.2177C>A (p.T726K) alteration is located in exon 11 (coding exon 10) of the NDST4 gene. This alteration results from a C to A substitution at nucleotide position 2177, causing the threonine (T) at amino acid position 726 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

0.27

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

Eigen

Benign

-0.11

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

M_CAP

Benign

0.0066

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.98

REVEL

Benign

0.15

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.023

Polyphen

0.019

Vest4

0.39

MutPred

0.48

Gain of methylation at T726 (P = 0.0188);

MVP

0.86

MPC

0.19

ClinPred

0.43

GERP RS

6.2

Varity_R

0.41

gMVP

0.49

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