3-143121534-G-C

Variant names:

• chr3-143121534-G-C
• rs767499387
• NM_004267.5:c.718G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004267.5(CHST2):​c.718G>C​(p.Gly240Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CHST2 NM_004267.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11
• Publications: 0 publications found

Genes affected

CHST2 (HGNC:1970): (carbohydrate sulfotransferase 2) This locus encodes a sulfotransferase protein. The encoded enzyme catalyzes the sulfation of a nonreducing N-acetylglucosamine residue, and may play a role in biosynthesis of 6-sulfosialyl Lewis X antigen. [provided by RefSeq, Aug 2011]

ENSG00000241679 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32263833).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004267.5. 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
	CHST2	NM_004267.5	MANE Select	c.718G>C	p.Gly240Arg	missense	Exon 2 of 2	NP_004258.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST2	ENST00000309575.5	TSL:1 MANE Select	c.718G>C	p.Gly240Arg	missense	Exon 2 of 2	ENSP00000307911.3	Q9Y4C5-1
	ENSG00000241679	ENST00000840528.1		n.361-30590G>C		intron	N/A
	ENSG00000241679	ENST00000840529.1		n.376-10184G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457602 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724660

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44492

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00 AC: 0 AN: 85868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109918

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.75	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.62	D
MutationAssessor	Benign	2.0	M
PhyloP100		3.1
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.88	N
REVEL	Uncertain	0.50
Sift	Benign	0.31	T
Sift4G	Benign	0.20	T
Polyphen		0.99	D
Vest4		0.079
MutPred		0.43		Gain of methylation at G240 (P = 0.0072)
MVP		0.97
MPC		2.3
ClinPred		0.84	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.73
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs767499387; hg19: chr3-142840376;