rs4148943

Variant names:

• chr10-72009749-C-T
• rs4148943
• NM_004273.5:c.*1278C>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.*1278C>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 0.435 in 152,322 control chromosomes in the GnomAD database, including 14,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14723 hom., cov: 33)
  • Exomes 𝑓: 0.43 (30 hom.)
• Consequence: CHST3 NM_004273.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.109
• Publications: 27 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=-0.65).
• BP6: Variant 10-72009749-C-T is Benign according to our data. Variant chr10-72009749-C-T is described in ClinVar as Benign. ClinVar VariationId is 300604.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.*1278C>T		3_prime_UTR	Exon 3 of 3	NP_004264.2
	CHST3	NM_001441201.1		c.*1278C>T		3_prime_UTR	Exon 3 of 3	NP_001428130.1
	CHST3	NM_001441202.1		c.*1278C>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.*1278C>T		3_prime_UTR	Exon 3 of 3	ENSP00000362207.4
	CHST3	ENST00000879006.1		c.*1278C>T		3_prime_UTR	Exon 3 of 3	ENSP00000549065.1
	CHST3	ENST00000943244.1		c.*1278C>T		3_prime_UTR	Exon 3 of 3	ENSP00000613303.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66145 AN: 151914 Hom.: 14709 Cov.: 33

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.450

GnomAD4 exome AF: 0.434 AC: 126 AN: 290 Hom.: 30 Cov.: 0 AF XY: 0.409 AC XY: 54 AN XY: 132

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.416 AC: 89 AN: 214

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.484 AC: 31 AN: 64

Other (OTH) AF: 0.667 AC: 4 AN: 6

GnomAD4 genome AF: 0.435 AC: 66190 AN: 152032 Hom.: 14723 Cov.: 33 AF XY: 0.427 AC XY: 31734 AN XY: 74300

African (AFR) AF: 0.430 AC: 17850 AN: 41470

American (AMR) AF: 0.414 AC: 6326 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1449 AN: 3468

East Asian (EAS) AF: 0.124 AC: 639 AN: 5160

South Asian (SAS) AF: 0.303 AC: 1457 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4522 AN: 10542

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.478 AC: 32489 AN: 67984

Other (OTH) AF: 0.444 AC: 937 AN: 2110

Alfa AF: 0.460 Hom.: 33193

Bravo AF: 0.434

Asia WGS AF: 0.221 AC: 772 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	-0.65
CADD	Benign	9.4
DANN	Benign	0.87
PhyloP100		-0.11
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: rs4148943; hg19: chr10-73769507;