Genetic Variant CHSY1:p.Glu779Lys (chr15-101177462-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_014918.5(CHSY1):c.2335G>A(p.Glu779Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000036 in 1,613,240 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: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CHSY1
NM_014918.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90

Publications

0 publications found

Variant links:

Genes affected

CHSY1 (HGNC:17198): (chondroitin sulfate synthase 1) This gene encodes a member of the chondroitin N-acetylgalactosaminyltransferase family. These enzymes possess dual glucuronyltransferase and galactosaminyltransferase activity and play critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan involved in many biological processes including cell proliferation and morphogenesis. Decreased expression of this gene may play a role in colorectal cancer, and mutations in this gene are a cause of temtamy preaxial brachydactyly syndrome. [provided by RefSeq, Dec 2011]

CHSY1 Gene-Disease associations (from GenCC):

temtamy preaxial brachydactyly syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet

CHSY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.42115268).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014918.5. 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
	CHSY1	NM_014918.5	MANE Select	c.2335G>A	p.Glu779Lys	missense	Exon 3 of 3	NP_055733.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.2335G>A	p.Glu779Lys	missense	Exon 3 of 3	ENSP00000254190.3	Q86X52
CHSY1	ENST00000968149.1		c.2329G>A	p.Glu777Lys	missense	Exon 3 of 3	ENSP00000638208.1
CHSY1	ENST00000543813.2	TSL:2	n.*1650G>A		non_coding_transcript_exon	Exon 3 of 3	ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.000223

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

249892

AF XY:

0.00000740

show subpopulations

Gnomad AFR exome

AF:

0.000308

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1460894

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726690

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33402

American (AMR)

AF:

0.000269

AC:

AN:

44534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

85930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111716

Other (OTH)

AF:

0.0000497

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000223

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41578

American (AMR)

AF:

0.00124

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.000434

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Temtamy preaxial brachydactyly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.0095

BayesDel_noAF

Uncertain

0.050

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.045

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.010

MetaRNN

Benign

0.42

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

5.9

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.3

REVEL

Benign

0.21

Sift

Benign

0.26

Sift4G

Benign

0.42

Polyphen

0.0070

Vest4

0.81

MVP

0.76

MPC

0.38

ClinPred

0.22

GERP RS

5.9

Varity_R

0.20

gMVP

0.60

Mutation Taster

=45/55

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over