rs4148941

Positions:

• chr10-72009234-C-A
• chr10-72009234-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004273.5(CHST3):​c.*763C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,052 control chromosomes in the GnomAD database, including 34,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (34216 hom., cov: 32)
  • Exomes 𝑓: 0.58 (7 hom.)
• Consequence: CHST3 NM_004273.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.23

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-72009234-C-A is Benign according to our data. Variant chr10-72009234-C-A is described in ClinVar as [Benign]. Clinvar id is 300581.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST3	NM_004273.5	c.*763C>A		3_prime_UTR_variant	3/3	ENST00000373115.5
CHST3	XM_006718075.5	c.*763C>A		3_prime_UTR_variant	3/3
CHST3	XM_011540369.3	c.*763C>A		3_prime_UTR_variant	3/3
CHST3	XM_047426022.1	c.*763C>A		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5	c.*763C>A		3_prime_UTR_variant	3/3	1	NM_004273.5	P1

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99766 AN: 151898 Hom.: 34167 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.649

GnomAD4 exome AF: 0.583 AC: 21 AN: 36 Hom.: 7 Cov.: 0 AF XY: 0.545 AC XY: 12 AN XY: 22

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.700

GnomAD4 genome AF: 0.657 AC: 99869 AN: 152016 Hom.: 34216 Cov.: 32 AF XY: 0.647 AC XY: 48037 AN XY: 74296

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.500

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.509

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.646

Alfa AF: 0.599 Hom.: 55941

Bravo AF: 0.674

Asia WGS AF: 0.501 AC: 1745 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Skeletal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spondyloepiphyseal dysplasia congenita Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Larsen syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.052
DANN	Benign	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

Other links and lift over

dbSNP: rs4148941; hg19: chr10-73768992;