rs535309495

Variant summary

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

The ENST00000373115.5(CHST3):ā€‹c.959C>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.00070 ( 0 hom., cov: 33)
Exomes š‘“: 0.000075 ( 0 hom. )

Consequence

CHST3
ENST00000373115.5 missense

Scores

19

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]

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
CHST3NM_004273.5 linkuse as main transcriptc.959C>G p.Thr320Ser missense_variant 3/3 ENST00000373115.5 NP_004264.2
CHST3XM_006718075.5 linkuse as main transcriptc.959C>G p.Thr320Ser missense_variant 3/3 XP_006718138.1
CHST3XM_011540369.3 linkuse as main transcriptc.959C>G p.Thr320Ser missense_variant 3/3 XP_011538671.1
CHST3XM_047426022.1 linkuse as main transcriptc.959C>G p.Thr320Ser missense_variant 3/3 XP_047281978.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CHST3ENST00000373115.5 linkuse as main transcriptc.959C>G p.Thr320Ser missense_variant 3/31 NM_004273.5 ENSP00000362207 P1

Frequencies

GnomAD3 genomes
AF:
0.000697
AC:
106
AN:
152188
Hom.:
0
Cov.:
33
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:
23
AN:
148336
Hom.:
0
AF XY:
0.000138
AC XY:
11
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.:
0
Cov.:
31
AF XY:
0.0000624
AC XY:
43
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.:
0
Cov.:
33
AF XY:
0.000604
AC XY:
45
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.:
0
Bravo
AF:
0.000729
ExAC
AF:
0.000167
AC:
11
Asia WGS
AF:
0.000289
AC:
1
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpNov 11, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
9.8
DANN
Benign
0.70
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.95
Eigen_PC
Benign
-0.80
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.0066
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.010
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.72
N
REVEL
Benign
0.18
Sift
Benign
0.75
T
Sift4G
Benign
0.87
T
Polyphen
0.0
B
Vest4
0.023
MutPred
0.42
Gain of disorder (P = 0.0655);
MVP
0.77
MPC
0.59
ClinPred
0.0016
T
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.

Other links and lift over

dbSNP: rs535309495; hg19: chr10-73767748; API