chr3-143121216-G-T

Variant names:

• chr3-143121216-G-T
• rs776782047
• NM_004267.5:c.400G>T

Variant summary

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

The NM_004267.5(CHST2):​c.400G>T​(p.Gly134Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G134R) 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: 0.225
• 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=0.32254297).

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.400G>T	p.Gly134Trp	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.400G>T	p.Gly134Trp	missense	Exon 2 of 2	ENSP00000307911.3	Q9Y4C5-1
	ENSG00000241679	ENST00000840528.1		n.361-30908G>T		intron	N/A
	ENSG00000241679	ENST00000840529.1		n.376-10502G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418938 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 703246

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32598

American (AMR) AF: 0.00 AC: 0 AN: 39126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24382

East Asian (EAS) AF: 0.00 AC: 0 AN: 38676

South Asian (SAS) AF: 0.00 AC: 0 AN: 81490

European-Finnish (FIN) AF: 0.0000230 AC: 1 AN: 43530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095042

Other (OTH) AF: 0.00 AC: 0 AN: 58704

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.075	D
MutationAssessor	Benign	0.0	N
PhyloP100		0.23
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.060	N
REVEL	Benign	0.27
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.69	P
Vest4		0.34
MutPred		0.38		Loss of loop (P = 0.0073)
MVP		0.89
MPC		1.2
ClinPred		0.29	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.38
Mutation Taster		=85/15	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: rs776782047; hg19: chr3-142840058;