10-72010315-C-T

Variant names:

• chr10-72010315-C-T
• rs4148946
• NM_004273.5:c.*1844C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004273.5(CHST3):​c.*1844C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,114 control chromosomes in the GnomAD database, including 30,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30677 hom., cov: 32)
  • Exomes 𝑓: 0.53 (6 hom.)
• Consequence: CHST3 NM_004273.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.42
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• spondyloepiphyseal dysplasia with congenital joint dislocations

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-72010315-C-T is Benign according to our data. Variant chr10-72010315-C-T is described in ClinVar as Benign. ClinVar VariationId is 300620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004273.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	NM_004273.5	MANE Select	c.*1844C>T		3_prime_UTR	Exon 3 of 3	NP_004264.2
	CHST3	NM_001441201.1		c.*1844C>T		3_prime_UTR	Exon 3 of 3	NP_001428130.1
	CHST3	NM_001441202.1		c.*1844C>T		3_prime_UTR	Exon 3 of 3	NP_001428131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	ENST00000373115.5	TSL:1 MANE Select	c.*1844C>T		3_prime_UTR	Exon 3 of 3	ENSP00000362207.4

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95419 AN: 151956 Hom.: 30637 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.525 AC: 21 AN: 40 Hom.: 6 Cov.: 0 AF XY: 0.577 AC XY: 15 AN XY: 26

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 18 AN: 36

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000649326), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.628 AC: 95511 AN: 152074 Hom.: 30677 Cov.: 32 AF XY: 0.620 AC XY: 46048 AN XY: 74328

African (AFR) AF: 0.770 AC: 31985 AN: 41512

American (AMR) AF: 0.604 AC: 9239 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1727 AN: 3468

East Asian (EAS) AF: 0.410 AC: 2121 AN: 5174

South Asian (SAS) AF: 0.509 AC: 2451 AN: 4818

European-Finnish (FIN) AF: 0.533 AC: 5633 AN: 10560

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40357 AN: 67946

Other (OTH) AF: 0.625 AC: 1319 AN: 2110

Alfa AF: 0.608 Hom.: 74183

Bravo AF: 0.641

Asia WGS AF: 0.496 AC: 1727 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Skeletal dysplasia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Spondyloepiphyseal dysplasia congenita Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Larsen syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Spondyloepiphyseal dysplasia with congenital joint dislocations Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.52
DANN	Benign	0.76
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4148946; hg19: chr10-73770073;