10-124044654-T-C

Variant names:

• chr10-124044654-T-C
• NM_001270764.2:c.812A>G

Variant summary

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

The NM_001270764.2(CHST15):​c.812A>G​(p.Asp271Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CHST15 NM_001270764.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.69

Genes affected

CHST15 (HGNC:18137): (carbohydrate sulfotransferase 15) Chondroitin sulfate (CS) is a glycosaminoglycan which is an important structural component of the extracellular matrix and which links to proteins to form proteoglycans. Chondroitin sulfate E (CS-E) is an isomer of chondroitin sulfate in which the C-4 and C-6 hydroxyl groups are sulfated. This gene encodes a type II transmembrane glycoprotein that acts as a sulfotransferase to transfer sulfate to the C-6 hydroxal group of chondroitin sulfate. This gene has also been identified as being co-expressed with RAG1 in B-cells and as potentially acting as a B-cell surface signaling receptor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST15	NM_001270764.2	c.812A>G	p.Asp271Gly	missense_variant	Exon 3 of 8	ENST00000435907.6	NP_001257693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST15	ENST00000435907.6	c.812A>G	p.Asp271Gly	missense_variant	Exon 3 of 8	1	NM_001270764.2	ENSP00000402394.1
CHST15	ENST00000346248.7	c.812A>G	p.Asp271Gly	missense_variant	Exon 3 of 8	1		ENSP00000333947.6
CHST15	ENST00000628426.1	c.812A>G	p.Asp271Gly	missense_variant	Exon 3 of 6	2		ENSP00000485905.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.812A>G (p.D271G) alteration is located in exon 3 (coding exon 2) of the CHST15 gene. This alteration results from a A to G substitution at nucleotide position 812, causing the aspartic acid (D) at amino acid position 271 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;.;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.57	D;D;D
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	L;L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-2.5	N;N;.
REVEL	Benign	0.22
Sift	Benign	0.18	T;T;.
Sift4G	Benign	0.20	T;T;T
Polyphen		0.34	B;B;D
Vest4		0.74
MutPred		0.57		Gain of methylation at R272 (P = 0.0334);Gain of methylation at R272 (P = 0.0334);Gain of methylation at R272 (P = 0.0334);
MVP		0.62
MPC		0.52
ClinPred		0.94	D
GERP RS		5.7
Varity_R		0.44
gMVP		0.91

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: chr10-125804170;