rs4148947

Variant names:

• chr10-72010359-T-C
• rs4148947
• NM_004273.5:c.*1888T>C

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.*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, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.174
• 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, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 300621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 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.*1888T>C		3_prime_UTR	Exon 3 of 3	NP_004264.2
	CHST3	NM_001441201.1		c.*1888T>C		3_prime_UTR	Exon 3 of 3	NP_001428130.1
	CHST3	NM_001441202.1		c.*1888T>C		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.*1888T>C		3_prime_UTR	Exon 3 of 3	ENSP00000362207.4	Q7LGC8
	CHST3	ENST00000879006.1		c.*1888T>C		3_prime_UTR	Exon 3 of 3	ENSP00000549065.1
	CHST3	ENST00000943244.1		c.*1888T>C		3_prime_UTR	Exon 3 of 3	ENSP00000613303.1

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

African (AFR) AF: 1.00 AC: 2 AN: 2

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) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.667 AC: 4 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.273 AC: 6 AN: 22

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.287 AC: 11894 AN: 41470

American (AMR) AF: 0.393 AC: 6007 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3468

East Asian (EAS) AF: 0.119 AC: 617 AN: 5174

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4541 AN: 10576

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.473 AC: 32161 AN: 67958

Other (OTH) AF: 0.412 AC: 872 AN: 2114

Alfa AF: 0.445 Hom.: 68664

Bravo AF: 0.384

Asia WGS AF: 0.202 AC: 704 AN: 3478

ClinVar

ClinVar submissions

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	-0.85
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.17
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: rs4148947; hg19: chr10-73770117;