10-124038598-C-A

Position:

• chr10-124038598-C-A

Variant summary

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

The NM_001270764.2(CHST15):​c.1107G>T​(p.Glu369Asp) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: CHST15 NM_001270764.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.825

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]

CHST15 (HGNC:):

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/exons	MANE	Protein	UniProt
CHST15	NM_001270764.2	c.1107G>T	p.Glu369Asp	missense_variant	5/8	ENST00000435907.6	NP_001257693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST15	ENST00000435907.6	c.1107G>T	p.Glu369Asp	missense_variant	5/8	1	NM_001270764.2	ENSP00000402394.1
CHST15	ENST00000346248.7	c.1107G>T	p.Glu369Asp	missense_variant	5/8	1		ENSP00000333947.6
CHST15	ENST00000628426.1	c.1107G>T	p.Glu369Asp	missense_variant	5/6	2		ENSP00000485905.1
CHST15	ENST00000476765.1	n.22G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.1107G>T (p.E369D) alteration is located in exon 5 (coding exon 4) of the CHST15 gene. This alteration results from a G to T substitution at nucleotide position 1107, causing the glutamic acid (E) at amino acid position 369 to be replaced by an aspartic acid (D). 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	0.62
BayesDel_addAF	Benign	0.0075	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T;T;.
Eigen	Benign	0.096
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M;M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.9	N;N;.
REVEL	Benign	0.18
Sift	Uncertain	0.023	D;D;.
Sift4G	Uncertain	0.027	D;D;D
Polyphen		0.14	B;B;P
Vest4		0.74
MutPred		0.65		Loss of catalytic residue at E369 (P = 0.1062);Loss of catalytic residue at E369 (P = 0.1062);Loss of catalytic residue at E369 (P = 0.1062);
MVP		0.43
MPC		0.92
ClinPred		0.95	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.77

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: chr10-125798114;