Genetic Variant CHST1:p.Gln2Glu (chr11-45650920-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003654.6(CHST1):c.4C>G(p.Gln2Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,377,840 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: 0.0000015 ( 0 hom. )

Consequence

CHST1
NM_003654.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.54

Variant links:

Genes affected

CHST1 (HGNC:1969): (carbohydrate sulfotransferase 1) This locus encodes a member of the keratin sulfotransferase family of proteins. The encoded enzyme catalyzes the sulfation of the proteoglycan keratin. [provided by RefSeq, Aug 2011]

CHST1 links:

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ACMG classification

Classification made for transcript

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=0.3979013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST1	NM_003654.6 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 4 of 4	ENST00000308064.7	NP_003645.1	O43916
CHST1	XM_006718356.5 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 4 of 5		XP_006718419.1
CHST1	XM_017018459.3 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 4 of 5		XP_016873948.1
CHST1	XM_047427781.1 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 4 of 4		XP_047283737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST1	ENST00000308064.7 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 4 of 4	1	NM_003654.6	ENSP00000309270.2		O43916

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

182270

Hom.:

AF XY:

0.0000208

AC XY:

AN XY:

96332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000233

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1377840

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675838

show subpopulations

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:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000170

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4C>G (p.Q2E) alteration is located in exon 1 (coding exon 1) of the CHST1 gene. This alteration results from a C to G substitution at nucleotide position 4, causing the glutamine (Q) at amino acid position 2 to be replaced by a glutamic acid (E). 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

0.081

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.23

Eigen

Benign

-0.12

Eigen_PC

Benign

0.093

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.036

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.080

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.36

REVEL

Benign

0.29

Sift

Benign

0.44

Sift4G

Benign

0.81

Polyphen

0.0080

Vest4

0.56

MutPred

0.19

Loss of MoRF binding (P = 0.0346);

MVP

0.73

MPC

1.0

ClinPred

0.65

GERP RS

4.4

Varity_R

0.13

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over