rs4148907

Variant names:

• chr10-71964508-C-G
• rs4148907
• NM_004273.5:c.-294C>G

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.-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, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.246
• Publications: 3 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=-0.8).
• BP6: Variant 10-71964508-C-G is Benign according to our data. Variant chr10-71964508-C-G is described in ClinVar as Benign. ClinVar VariationId is 300548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.661 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.-294C>G		5_prime_UTR	Exon 1 of 3	NP_004264.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	ENST00000373115.5	TSL:1 MANE Select	c.-294C>G		5_prime_UTR	Exon 1 of 3	ENSP00000362207.4	Q7LGC8

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.625 AC: 20 AN: 32

Other (OTH) AF: 0.500 AC: 2 AN: 4

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

African (AFR) AF: 0.668 AC: 27714 AN: 41506

American (AMR) AF: 0.563 AC: 8604 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2185 AN: 5126

South Asian (SAS) AF: 0.528 AC: 2548 AN: 4824

European-Finnish (FIN) AF: 0.580 AC: 6112 AN: 10534

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.616 AC: 41860 AN: 67910

Other (OTH) AF: 0.614 AC: 1297 AN: 2114

Alfa AF: 0.624 Hom.: 3682

Bravo AF: 0.615

Asia WGS AF: 0.486 AC: 1679 AN: 3456

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	-0.80
CADD	Benign	8.4
DANN	Benign	0.77
PhyloP100		-0.25
PromoterAI		0.10	Neutral
Mutation Taster		=300/0	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: rs4148907; hg19: chr10-73724266;