10-72005861-T-A

Variant names:

• chr10-72005861-T-A
• NM_004273.5:c.19T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004273.5(CHST3):​c.19T>A​(p.Leu7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST3 NM_004273.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.383

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16187078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST3	NM_004273.5	c.19T>A	p.Leu7Met	missense_variant	Exon 2 of 3	ENST00000373115.5	NP_004264.2
CHST3	XM_006718075.5	c.19T>A	p.Leu7Met	missense_variant	Exon 2 of 3		XP_006718138.1
CHST3	XM_011540369.3	c.19T>A	p.Leu7Met	missense_variant	Exon 2 of 3		XP_011538671.1
CHST3	XM_047426022.1	c.19T>A	p.Leu7Met	missense_variant	Exon 2 of 3		XP_047281978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5	c.19T>A	p.Leu7Met	missense_variant	Exon 2 of 3	1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spondyloepiphyseal dysplasia with congenital joint dislocations Uncertain:1

Feb 24, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 7 of the CHST3 protein (p.Leu7Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHST3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1477983). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	0.81	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.21
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.052	T
Polyphen		0.23	B
Vest4		0.27
MutPred		0.21		Gain of disorder (P = 0.0771);
MVP		0.78
MPC		0.97
ClinPred		0.22	T
GERP RS		-4.5
Varity_R		0.086
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-73765619;