rs751450

Variant names:

• chr10-72001257-A-G
• rs751450
• NM_004273.5:c.-107-4479A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004273.5(CHST3):​c.-107-4479A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,994 control chromosomes in the GnomAD database, including 34,206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34206 hom., cov: 31)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST3	NM_004273.5	c.-107-4479A>G		intron_variant	Intron 1 of 2	ENST00000373115.5	NP_004264.2
CHST3	NM_001441201.1	c.-107-4479A>G		intron_variant	Intron 1 of 2		NP_001428130.1
CHST3	NM_001441202.1	c.-107-4479A>G		intron_variant	Intron 1 of 2		NP_001428131.1
CHST3	XM_011540369.3	c.-107-4479A>G		intron_variant	Intron 1 of 2		XP_011538671.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5	c.-107-4479A>G		intron_variant	Intron 1 of 2	1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99734 AN: 151876 Hom.: 34160 Cov.: 31

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.657 AC: 99831 AN: 151994 Hom.: 34206 Cov.: 31 AF XY: 0.646 AC XY: 47983 AN XY: 74288

African (AFR) AF: 0.870 AC: 36113 AN: 41494

American (AMR) AF: 0.618 AC: 9448 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1748 AN: 3470

East Asian (EAS) AF: 0.420 AC: 2161 AN: 5150

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4810

European-Finnish (FIN) AF: 0.539 AC: 5685 AN: 10544

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40463 AN: 67940

Other (OTH) AF: 0.643 AC: 1355 AN: 2108

Alfa AF: 0.609 Hom.: 47755

Bravo AF: 0.674

Asia WGS AF: 0.476 AC: 1658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.99
DANN	Benign	0.44
PhyloP100		-0.34
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: rs751450; hg19: chr10-73761015;