10-72005455-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004273.5(CHST3):c.-107-281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,056 control chromosomes in the GnomAD database, including 11,851 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (11851 hom., cov: 33)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0380

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-72005455-T-C is Benign according to our data. Variant chr10-72005455-T-C is described in ClinVar as [Benign]. Clinvar id is 1254668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST3	NM_004273.5	c.-107-281T>C		intron_variant		ENST00000373115.5
CHST3	XM_006718075.5	c.-107-281T>C		intron_variant
CHST3	XM_011540369.3	c.-107-281T>C		intron_variant
CHST3	XM_047426022.1	c.-107-281T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5	c.-107-281T>C		intron_variant		1	NM_004273.5	P1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57669 AN: 151938 Hom.: 11845 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.410

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.379 AC: 57678 AN: 152056 Hom.: 11851 Cov.: 33 AF XY: 0.374 AC XY: 27801 AN XY: 74318

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.397

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.404

Alfa AF: 0.439 Hom.: 3087

Bravo AF: 0.370

Asia WGS AF: 0.201 AC: 701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.4
Dann	Benign	0.46

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: rs4747235; hg19: chr10-73765213;