3-143120979-G-A

Position:

• chr3-143120979-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004267.5(CHST2):​c.163G>A​(p.Ala55Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000431 in 1,391,950 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: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CHST2 NM_004267.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.69

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4073983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST2	NM_004267.5	c.163G>A	p.Ala55Thr	missense_variant	2/2	ENST00000309575.5	NP_004258.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST2	ENST00000309575.5	c.163G>A	p.Ala55Thr	missense_variant	2/2	1	NM_004267.5	ENSP00000307911	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000431 AC: 6 AN: 1391950 Hom.: 0 Cov.: 31 AF XY: 0.00000291 AC XY: 2 AN XY: 687662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000556

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.163G>A (p.A55T) alteration is located in exon 2 (coding exon 1) of the CHST2 gene. This alteration results from a G to A substitution at nucleotide position 163, causing the alanine (A) at amino acid position 55 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.87	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.95	D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.39	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.019	D
Sift4G	Benign	0.18	T
Polyphen		0.94	P
Vest4		0.23
MutPred		0.30		Loss of helix (P = 0.0072);
MVP		0.94
MPC		1.2
ClinPred		0.70	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-142839821;