rs4148947

chr10-72010359-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004273.5(CHST3):c.*1888T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 152,106 control chromosomes in the GnomAD database, including 12,226 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (12221 hom., cov: 32)
  • Exomes 𝑓: 0.41 (5 hom.)
• Consequence: CHST3 NM_004273.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:4
• Conservation: PhyloP100: 0.174

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-72010359-T-C is Benign according to our data. Variant chr10-72010359-T-C is described in ClinVar as [Benign]. Clinvar id is 300621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST3	NM_004273.5	c.*1888T>C		3_prime_UTR_variant	3/3	ENST00000373115.5
CHST3	XM_006718075.5	c.*1888T>C		3_prime_UTR_variant	3/3
CHST3	XM_011540369.3	c.*1888T>C		3_prime_UTR_variant	3/3
CHST3	XM_047426022.1	c.*1888T>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5	c.*1888T>C		3_prime_UTR_variant	3/3	1	NM_004273.5	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59362 AN: 151954 Hom.: 12211 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.412 AC: 14 AN: 34 Hom.: 5 Cov.: 0 AF XY: 0.357 AC XY: 10 AN XY: 28

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.273

GnomAD4 genome AF: 0.391 AC: 59394 AN: 152072 Hom.: 12221 Cov.: 32 AF XY: 0.385 AC XY: 28592 AN XY: 74344

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.412

Alfa AF: 0.455 Hom.: 33627

Bravo AF: 0.384

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

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

- -

Spondyloepiphyseal dysplasia with congenital joint dislocations 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	-0.85
Cadd	Benign	11
Dann	Benign	0.63

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: rs4148947; hg19: chr10-73770117;