Variant rs535309495 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_004273.5(CHST3):c.959C>G(p.Thr320Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000136 in 1,549,568 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

CHST3
NM_004273.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.302

Variant links:

Genes affected

CHST3 (HGNC:1971): (carbohydrate sulfotransferase 3) This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. [provided by RefSeq, Mar 2009]

CHST3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0066131055).

BP6

Variant 10-72007990-C-G is Benign according to our data. Variant chr10-72007990-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 533430.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000696 (106/152306) while in subpopulation AFR AF= 0.00243 (101/41576). AF 95% confidence interval is 0.00204. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST3	NM_004273.5 linkuse as main transcript	c.959C>G	p.Thr320Ser	missense_variant	3/3	ENST00000373115.5	NP_004264.2	Q7LGC8
CHST3	XM_006718075.5 linkuse as main transcript	c.959C>G	p.Thr320Ser	missense_variant	3/3		XP_006718138.1	Q7LGC8
CHST3	XM_011540369.3 linkuse as main transcript	c.959C>G	p.Thr320Ser	missense_variant	3/3		XP_011538671.1	Q7LGC8
CHST3	XM_047426022.1 linkuse as main transcript	c.959C>G	p.Thr320Ser	missense_variant	3/3		XP_047281978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5 linkuse as main transcript	c.959C>G	p.Thr320Ser	missense_variant	3/3	1	NM_004273.5	ENSP00000362207.4		Q7LGC8

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000155

AC:

AN:

148336

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

79494

show subpopulations

Gnomad AFR exome

AF:

0.00237

Gnomad AMR exome

AF:

0.000163

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:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000751

AC:

105

AN:

1397262

Hom.:

Cov.:

AF XY:

0.0000624

AC XY:

AN XY:

689172

show subpopulations

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.000140

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:

0.00000464

Gnomad4 OTH exome

AF:

0.000173

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152306

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000729

ExAC

AF:

0.000167

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3470

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

9.8

DANN

Benign

0.70

DEOGEN2

Benign

0.12

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.52

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0066

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.010

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.72

REVEL

Benign

0.18

Sift

Benign

0.75

Sift4G

Benign

0.87

Polyphen

0.0

Vest4

0.023

MutPred

0.42

Gain of disorder (P = 0.0655);

MVP

0.77

MPC

0.59

ClinPred

0.0016

GERP RS

-0.039

Varity_R

0.054

gMVP

0.57

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