10-71964508-C-G

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.-294C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 152,010 control chromosomes in the GnomAD database, including 28,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (28749 hom., cov: 34)
  • Exomes 𝑓: 0.58 (6 hom.)
• Consequence: CHST3 NM_004273.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:4
• Conservation: PhyloP100: -0.246

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=-0.8).
• BP6: Variant 10-71964508-C-G is Benign according to our data. Variant chr10-71964508-C-G is described in ClinVar as [Benign]. Clinvar id is 300548.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-71964508-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST3	NM_004273.5	c.-294C>G		5_prime_UTR_variant	1/3	ENST00000373115.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5	c.-294C>G		5_prime_UTR_variant	1/3	1	NM_004273.5	P1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93014 AN: 151864 Hom.: 28716 Cov.: 34

Gnomad AFR AF: 0.667

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.613

GnomAD4 exome AF: 0.579 AC: 22 AN: 38 Hom.: 6 Cov.: 0 AF XY: 0.607 AC XY: 17 AN XY: 28

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.625

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.613 AC: 93085 AN: 151972 Hom.: 28749 Cov.: 34 AF XY: 0.604 AC XY: 44884 AN XY: 74262

Gnomad4 AFR AF: 0.668

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.614

Alfa AF: 0.624 Hom.: 3682

Bravo AF: 0.615

Asia WGS AF: 0.486 AC: 1679 AN: 3456

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	-0.80
Cadd	Benign	8.4
Dann	Benign	0.77

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: rs4148907; hg19: chr10-73724266;