Variant 4-114833675-G-A 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.2327C>T(p.Ala776Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,612,806 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NDST4
NM_022569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24749011).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST4	NM_022569.3 linkuse as main transcript	c.2327C>T	p.Ala776Val	missense_variant	12/14	ENST00000264363.7	NP_072091.1	Q9H3R1-1A8K0V5
NDST4	XM_017008545.3 linkuse as main transcript	c.1190C>T	p.Ala397Val	missense_variant	11/13		XP_016864034.1
NDST4	XM_017008546.2 linkuse as main transcript	c.1190C>T	p.Ala397Val	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.2327C>T	p.Ala776Val	missense_variant	12/14	1	NM_022569.3	ENSP00000264363.2	Q9H3R1-1
NDST4	ENST00000504854.1 linkuse as main transcript	n.*178C>T		non_coding_transcript_exon_variant	11/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000504854.1 linkuse as main transcript	n.*178C>T		3_prime_UTR_variant	11/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000613194 linkuse as main transcript	c.*178C>T		3_prime_UTR_variant	13/15	5		ENSP00000483949.1	Q9H3R1-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152206

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000800

AC:

AN:

250036

Hom.:

AF XY:

0.0000814

AC XY:

AN XY:

135158

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000587

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:

0.000150

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1460600

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

726610

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000674

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:

0.0000477

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000404

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

Bravo

AF:

0.000110

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

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 07, 2024

The c.2327C>T (p.A776V) alteration is located in exon 12 (coding exon 11) of the NDST4 gene. This alteration results from a C to T substitution at nucleotide position 2327, causing the alanine (A) at amino acid position 776 to be replaced by a valine (V). 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

0.092

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Benign

0.065

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.038

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.89

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.14

REVEL

Uncertain

0.35

Sift

Benign

0.43

Sift4G

Benign

1.0

Polyphen

0.37

Vest4

0.35

MVP

0.77

MPC

0.66

ClinPred

0.17

GERP RS

5.1

Varity_R

0.25

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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