rs372003076

Variant names:

• chr10-124021369-C-A
• rs372003076
• NM_001270764.2:c.1234G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-124021369-C-A
• chr10-124021369-C-T

Variant summary

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

The NM_001270764.2(CHST15):​c.1234G>T​(p.Ala412Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A412T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHST15 NM_001270764.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21700087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST15	NM_001270764.2	c.1234G>T	p.Ala412Ser	missense_variant	Exon 6 of 8	ENST00000435907.6	NP_001257693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST15	ENST00000435907.6	c.1234G>T	p.Ala412Ser	missense_variant	Exon 6 of 8	1	NM_001270764.2	ENSP00000402394.1
CHST15	ENST00000346248.7	c.1234G>T	p.Ala412Ser	missense_variant	Exon 6 of 8	1		ENSP00000333947.6
CHST15	ENST00000628426.1	c.1234G>T	p.Ala412Ser	missense_variant	Exon 6 of 6	2		ENSP00000485905.1
CHST15	ENST00000476765.1	n.149G>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T;T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T;.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.8	L;L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N;N;.
REVEL	Benign	0.11
Sift	Benign	0.33	T;T;.
Sift4G	Benign	0.069	T;T;T
Polyphen		0.69	P;P;P
Vest4		0.40
MutPred		0.53		Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);Gain of disorder (P = 0.0447);
MVP		0.49
MPC		0.39
ClinPred		0.92	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs372003076; hg19: chr10-125780885;