rs4148950

Positions:

• chr10-72011948-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004273.5(CHST3):​c.*3477G>A 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 152,142 control chromosomes in the GnomAD database, including 12,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12257 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST3 NM_004273.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.540

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-72011948-G-A is Benign according to our data. Variant chr10-72011948-G-A is described in ClinVar as [Benign]. Clinvar id is 300649.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST3	NM_004273.5	c.*3477G>A		3_prime_UTR_variant	3/3	ENST00000373115.5	NP_004264.2
CHST3	XM_006718075.5	c.*3477G>A		3_prime_UTR_variant	3/3		XP_006718138.1
CHST3	XM_011540369.3	c.*3477G>A		3_prime_UTR_variant	3/3		XP_011538671.1
CHST3	XM_047426022.1	c.*3477G>A		3_prime_UTR_variant	3/3		XP_047281978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5	c.*3477G>A		3_prime_UTR_variant	3/3	1	NM_004273.5	ENSP00000362207	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59490 AN: 152024 Hom.: 12247 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.419

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.391 AC: 59522 AN: 152142 Hom.: 12257 Cov.: 33 AF XY: 0.385 AC XY: 28652 AN XY: 74394

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.413

Alfa AF: 0.455 Hom.: 33634

Bravo AF: 0.384

Asia WGS AF: 0.200 AC: 697 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Skeletal dysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Spondyloepiphyseal dysplasia congenita Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Larsen syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Spondyloepiphyseal dysplasia with congenital joint dislocations Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs4148950; hg19: chr10-73771706;