Genetic Variant CHSY1:p.Thr734Thr (chr15-101177595-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_014918.5(CHSY1):c.2202G>A(p.Thr734Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,614,192 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 Benign (★).

Frequency

Genomes: 𝑓 0.00065 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

CHSY1
NM_014918.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.872

Publications

1 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet

CHSY1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 15-101177595-C-T is Benign according to our data. Variant chr15-101177595-C-T is described in ClinVar as [Benign]. Clinvar id is 2152911.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.872 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5 link	c.2202G>A	p.Thr734Thr	synonymous_variant	Exon 3 of 3	ENST00000254190.4	NP_055733.2	Q86X52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHSY1	ENST00000254190.4 link	c.2202G>A	p.Thr734Thr	synonymous_variant	Exon 3 of 3	1	NM_014918.5	ENSP00000254190.3	Q86X52
CHSY1	ENST00000543813.2 link	n.*1517G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7
CHSY1	ENST00000543813.2 link	n.*1517G>A		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.00

GnomAD2 exomes

AF:

0.000211

AC:

AN:

251466

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00227

AC:

AN:

33480

American (AMR)

AF:

0.000201

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1112010

Other (OTH)

AF:

0.000132

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000650

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41558

American (AMR)

AF:

0.000196

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.000748

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Temtamy preaxial brachydactyly syndrome

Benign:1

Apr 18, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.10

(source)

DANN

Benign

0.49

PhyloP100

-0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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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15-101177595-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over