NM_001270764.2:c.847G>T

Variant names:

• chr10-124044619-C-A
• rs780219214
• NM_001270764.2:c.847G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270764.2(CHST15):​c.847G>T​(p.Ala283Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000561 in 1,425,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: CHST15 NM_001270764.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22543523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270764.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST15	NM_001270764.2	MANE Select	c.847G>T	p.Ala283Ser	missense	Exon 3 of 8	NP_001257693.1	Q7LFX5-1
	CHST15	NM_015892.5		c.847G>T	p.Ala283Ser	missense	Exon 3 of 8	NP_056976.2
	CHST15	NM_001270765.2		c.847G>T	p.Ala283Ser	missense	Exon 3 of 6	NP_001257694.1	Q7LFX5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST15	ENST00000435907.6	TSL:1 MANE Select	c.847G>T	p.Ala283Ser	missense	Exon 3 of 8	ENSP00000402394.1	Q7LFX5-1
	CHST15	ENST00000346248.7	TSL:1	c.847G>T	p.Ala283Ser	missense	Exon 3 of 8	ENSP00000333947.6	Q7LFX5-1
	CHST15	ENST00000874549.1		c.847G>T	p.Ala283Ser	missense	Exon 3 of 8	ENSP00000544608.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000134 AC: 3 AN: 223892 AF XY: 0.0000164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000631

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000561 AC: 8 AN: 1425414 Hom.: 0 Cov.: 31 AF XY: 0.00000850 AC XY: 6 AN XY: 706032

African (AFR) AF: 0.00 AC: 0 AN: 31696

American (AMR) AF: 0.00 AC: 0 AN: 39912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24622

East Asian (EAS) AF: 0.00 AC: 0 AN: 37520

South Asian (SAS) AF: 0.0000724 AC: 6 AN: 82904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5642

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1091822

Other (OTH) AF: 0.00 AC: 0 AN: 58706

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.44	N
PhyloP100		4.6
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.098
Sift	Benign	0.31	T
Sift4G	Benign	0.49	T
Polyphen		0.57	P
Vest4		0.35
MutPred		0.42		Gain of disorder (P = 0.0249)
MVP		0.52
MPC		0.35
ClinPred		0.20	T
GERP RS		5.7
Varity_R		0.17
gMVP		0.72
Mutation Taster		=93/7	polymorphism

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: rs780219214; hg19: chr10-125804135;