NM_004273.5:c.-108+5046C>T

Variant names:

• chr10-71969740-C-T
• rs4148912
• NM_004273.5:c.-108+5046C>T

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+5046C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,034 control chromosomes in the GnomAD database, including 29,270 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 0.60 (29270 hom., cov: 32)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST3	NM_004273.5	c.-108+5046C>T		intron_variant	Intron 1 of 2	ENST00000373115.5	NP_004264.2
CHST3	NM_001441201.1	c.-108+4265C>T		intron_variant	Intron 1 of 2		NP_001428130.1
CHST3	NM_001441202.1	c.-108+4840C>T		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+5046C>T		intron_variant	Intron 1 of 2	1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90473 AN: 151916 Hom.: 29263 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.708

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.595 AC: 90508 AN: 152034 Hom.: 29270 Cov.: 32 AF XY: 0.600 AC XY: 44582 AN XY: 74334

African (AFR) AF: 0.319 AC: 13243 AN: 41454

American (AMR) AF: 0.646 AC: 9880 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2320 AN: 3470

East Asian (EAS) AF: 0.758 AC: 3907 AN: 5156

South Asian (SAS) AF: 0.766 AC: 3688 AN: 4814

European-Finnish (FIN) AF: 0.683 AC: 7229 AN: 10584

Middle Eastern (MID) AF: 0.710 AC: 206 AN: 290

European-Non Finnish (NFE) AF: 0.707 AC: 48050 AN: 67960

Other (OTH) AF: 0.627 AC: 1324 AN: 2110

Alfa AF: 0.675 Hom.: 64721

Bravo AF: 0.579

Asia WGS AF: 0.739 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.64
DANN	Benign	0.58
PhyloP100		-1.3
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: rs4148912; hg19: chr10-73729498;