10-72013004-C-T

Variant names:

• chr10-72013004-C-T
• rs730720
• NM_004273.5:c.*4533C>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.*4533C>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 0.436 in 152,080 control chromosomes in the GnomAD database, including 14,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14774 hom., cov: 32)
  • Exomes 𝑓: 0.37 (2 hom.)
• Consequence: CHST3 NM_004273.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.482
• Publications: 25 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-72013004-C-T is Benign according to our data. Variant chr10-72013004-C-T is described in ClinVar as Benign. ClinVar VariationId is 300675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	NM_004273.5	MANE Select	c.*4533C>T		3_prime_UTR	Exon 3 of 3	NP_004264.2
	CHST3	NM_001441201.1		c.*4533C>T		3_prime_UTR	Exon 3 of 3	NP_001428130.1
	CHST3	NM_001441202.1		c.*4533C>T		3_prime_UTR	Exon 3 of 3	NP_001428131.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	ENST00000373115.5	TSL:1 MANE Select	c.*4533C>T		3_prime_UTR	Exon 3 of 3	ENSP00000362207.4	Q7LGC8
	CHST3	ENST00000879006.1		c.*4533C>T		3_prime_UTR	Exon 3 of 3	ENSP00000549065.1
	CHST3	ENST00000943244.1		c.*4533C>T		3_prime_UTR	Exon 3 of 3	ENSP00000613303.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66290 AN: 151932 Hom.: 14758 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.452

GnomAD4 exome AF: 0.367 AC: 11 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.318 AC XY: 7 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.318 AC: 7 AN: 22

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.436 AC: 66337 AN: 152050 Hom.: 14774 Cov.: 32 AF XY: 0.428 AC XY: 31821 AN XY: 74326

African (AFR) AF: 0.433 AC: 17962 AN: 41454

American (AMR) AF: 0.414 AC: 6332 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3470

East Asian (EAS) AF: 0.124 AC: 643 AN: 5174

South Asian (SAS) AF: 0.303 AC: 1459 AN: 4822

European-Finnish (FIN) AF: 0.431 AC: 4550 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.478 AC: 32482 AN: 67964

Other (OTH) AF: 0.446 AC: 939 AN: 2104

Alfa AF: 0.460 Hom.: 59221

Bravo AF: 0.435

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Larsen syndrome (1)
-	-	1	not provided (1)
-	-	1	Skeletal dysplasia (1)
-	-	1	Spondyloepiphyseal dysplasia congenita (1)
-	-	1	Spondyloepiphyseal dysplasia with congenital joint dislocations (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.62
DANN	Benign	0.57
PhyloP100		-0.48
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: rs730720; hg19: chr10-73772762;