rs874692

chr10-71970315-A-Gchr10-71970315-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004273.5(CHST3):c.-108+5621A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,150 control chromosomes in the GnomAD database, including 57,209 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 0.86 (57209 hom., cov: 31)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST3	NM_004273.5	c.-108+5621A>G		intron_variant		ENST00000373115.5
CHST3	XM_006718075.5	c.-108+4840A>G		intron_variant
CHST3	XM_047426022.1	c.-108+5415A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5	c.-108+5621A>G		intron_variant		1	NM_004273.5	P1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131486 AN: 152032 Hom.: 57151 Cov.: 31

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.837

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.865 AC: 131602 AN: 152150 Hom.: 57209 Cov.: 31 AF XY: 0.861 AC XY: 64048 AN XY: 74364

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.837

Gnomad4 OTH AF: 0.862

Alfa AF: 0.838 Hom.: 68654

Bravo AF: 0.868

Asia WGS AF: 0.824 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	18
Dann	Benign	0.88

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: rs874692; hg19: chr10-73730073;