Variant 4-114848294-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022569.3(NDST4):c.1861A>G(p.Ile621Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,608,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

NDST4
NM_022569.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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 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=0.013890088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDST4	NM_022569.3 linkuse as main transcript	c.1861A>G	p.Ile621Val	missense_variant	9/14	ENST00000264363.7	NP_072091.1	Q9H3R1-1A8K0V5
NDST4	XM_017008545.3 linkuse as main transcript	c.724A>G	p.Ile242Val	missense_variant	8/13		XP_016864034.1
NDST4	XM_017008546.2 linkuse as main transcript	c.724A>G	p.Ile242Val	missense_variant	7/12		XP_016864035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDST4	ENST00000264363.7 linkuse as main transcript	c.1861A>G	p.Ile621Val	missense_variant	9/14	1	NM_022569.3	ENSP00000264363.2	Q9H3R1-1
NDST4	ENST00000504854.1 linkuse as main transcript	n.724A>G		non_coding_transcript_exon_variant	7/13	1		ENSP00000423218.1	Q9H3R1-2
NDST4	ENST00000613194.4 linkuse as main transcript	c.724A>G	p.Ile242Val	missense_variant	9/15	5		ENSP00000483949.1	Q9H3R1-2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00346

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:

0.000294

AC:

AN:

248056

Hom.:

AF XY:

0.000224

AC XY:

AN XY:

134094

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00601

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.000660

GnomAD4 exome

AF:

0.000145

AC:

211

AN:

1456278

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

724646

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000457

Gnomad4 ASJ exome

AF:

0.00603

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.000449

GnomAD4 genome

AF:

0.000125

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00346

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:

0.000362

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.00

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

Jul 12, 2022

The c.1861A>G (p.I621V) alteration is located in exon 9 (coding exon 8) of the NDST4 gene. This alteration results from a A to G substitution at nucleotide position 1861, causing the isoleucine (I) at amino acid position 621 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

0.061

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.70

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.23

N;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.49

N;.

REVEL

Benign

0.027

Sift

Benign

0.49

T;.

Sift4G

Benign

0.46

T;T

Polyphen

0.0

B;.

Vest4

0.23

MVP

0.60

MPC

0.14

ClinPred

0.016

GERP RS

1.3

Varity_R

0.031

gMVP

0.25

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