chr10-71969994-A-G

Variant names:

• chr10-71969994-A-G
• rs4148913
• NM_004273.5:c.-108+5300A>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.-108+5300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,112 control chromosomes in the GnomAD database, including 16,488 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 0.46 (16488 hom., cov: 34)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 3 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST3	NM_004273.5	c.-108+5300A>G		intron_variant	Intron 1 of 2	ENST00000373115.5	NP_004264.2
CHST3	NM_001441201.1	c.-108+4519A>G		intron_variant	Intron 1 of 2		NP_001428130.1
CHST3	NM_001441202.1	c.-108+5094A>G		intron_variant	Intron 1 of 2		NP_001428131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5	c.-108+5300A>G		intron_variant	Intron 1 of 2	1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69759 AN: 151994 Hom.: 16456 Cov.: 34

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.459 AC: 69833 AN: 152112 Hom.: 16488 Cov.: 34 AF XY: 0.453 AC XY: 33656 AN XY: 74358

African (AFR) AF: 0.566 AC: 23481 AN: 41470

American (AMR) AF: 0.411 AC: 6286 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1412 AN: 3470

East Asian (EAS) AF: 0.252 AC: 1301 AN: 5170

South Asian (SAS) AF: 0.401 AC: 1935 AN: 4826

European-Finnish (FIN) AF: 0.400 AC: 4236 AN: 10586

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29550 AN: 67982

Other (OTH) AF: 0.467 AC: 984 AN: 2106

Alfa AF: 0.440 Hom.: 18890

Bravo AF: 0.465

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4148913; hg19: chr10-73729752;