chr10-72011948-G-A

Variant names:

• chr10-72011948-G-A
• rs4148950
• NM_004273.5:c.*3477G>A

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.*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
• Publications: 24 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=-0.9).
• BP6: Variant 10-72011948-G-A is Benign according to our data. Variant chr10-72011948-G-A is described in ClinVar as Benign. ClinVar VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	NM_004273.5	MANE Select	c.*3477G>A		3_prime_UTR	Exon 3 of 3	NP_004264.2
	CHST3	NM_001441201.1		c.*3477G>A		3_prime_UTR	Exon 3 of 3	NP_001428130.1
	CHST3	NM_001441202.1		c.*3477G>A		3_prime_UTR	Exon 3 of 3	NP_001428131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST3	ENST00000373115.5	TSL:1 MANE Select	c.*3477G>A		3_prime_UTR	Exon 3 of 3	ENSP00000362207.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

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: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.290 AC: 12044 AN: 41500

American (AMR) AF: 0.393 AC: 6000 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3468

East Asian (EAS) AF: 0.110 AC: 572 AN: 5180

South Asian (SAS) AF: 0.299 AC: 1444 AN: 4830

European-Finnish (FIN) AF: 0.430 AC: 4548 AN: 10582

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32180 AN: 67988

Other (OTH) AF: 0.413 AC: 873 AN: 2112

Alfa AF: 0.445 Hom.: 69566

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Spondyloepiphyseal dysplasia congenita Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Larsen syndrome Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Spondyloepiphyseal dysplasia with congenital joint dislocations Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.32
PhyloP100		-0.54
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: rs4148950; hg19: chr10-73771706;