Genetic Variant NM_003654.6:c.4C>G (chr11-45650920-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 12/21 in silico tools predict 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

Publications

0 publications found

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 was made for transcript

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=0.3979013).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003654.6. 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
	CHST1	NM_003654.6	MANE Select	c.4C>G	p.Gln2Glu	missense	Exon 4 of 4	NP_003645.1	O43916

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHST1	ENST00000308064.7	TSL:1 MANE Select	c.4C>G	p.Gln2Glu	missense	Exon 4 of 4	ENSP00000309270.2	O43916
CHST1	ENST00000891796.1		c.4C>G	p.Gln2Glu	missense	Exon 4 of 4	ENSP00000561855.1
CHST1	ENST00000891797.1		c.4C>G	p.Gln2Glu	missense	Exon 4 of 4	ENSP00000561856.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

182270

AF XY:

0.0000208

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 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

African (AFR)

AF:

0.00

AC:

AN:

31056

American (AMR)

AF:

0.00

AC:

AN:

32760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20478

East Asian (EAS)

AF:

0.00

AC:

AN:

38960

South Asian (SAS)

AF:

0.00

AC:

AN:

72266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49516

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5348

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1070790

Other (OTH)

AF:

0.00

AC:

AN:

56666

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000170

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

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

PhyloP100

9.5

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

Mutation Taster

=66/34

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over