3-143121937-A-G

Variant names:

• chr3-143121937-A-G
• rs745494221
• NM_004267.5:c.1121A>G

Variant summary

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

The NM_004267.5(CHST2):​c.1121A>G​(p.His374Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,427,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. H374P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CHST2 NM_004267.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.14
• 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 2 ACMG points.

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

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.1121A>G	p.His374Arg	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.1121A>G	p.His374Arg	missense	Exon 2 of 2	ENSP00000307911.3	Q9Y4C5-1
	ENSG00000241679	ENST00000840528.1		n.361-30187A>G		intron	N/A
	ENSG00000241679	ENST00000840529.1		n.376-9781A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1427852 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 707038

African (AFR) AF: 0.00 AC: 0 AN: 32354

American (AMR) AF: 0.00 AC: 0 AN: 40174

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23788

East Asian (EAS) AF: 0.00 AC: 0 AN: 39348

South Asian (SAS) AF: 0.00 AC: 0 AN: 81518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5590

European-Non Finnish (NFE) AF: 9.13e-7 AC: 1 AN: 1095026

Other (OTH) AF: 0.00 AC: 0 AN: 58682

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	0.81	L
PhyloP100		5.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.71	N
REVEL	Pathogenic	0.69
Sift	Benign	0.16	T
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.54
MutPred		0.47		Gain of MoRF binding (P = 0.0068)
MVP		0.99
MPC		2.4
ClinPred		0.84	D
GERP RS		4.5
Varity_R		0.16
gMVP		0.78
Mutation Taster		=40/60	disease causing

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: rs745494221; hg19: chr3-142840779;