15-101178472-A-G

Position:

chr15-101178472-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014918.5(CHSY1):c.1325T>C(p.Met442Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00578 in 1,614,166 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 41 hom. )

Consequence

CHSY1
NM_014918.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 6.05

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010369569).

BP6

Variant 15-101178472-A-G is Benign according to our data. Variant chr15-101178472-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 281557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHSY1	NM_014918.5 linkuse as main transcript	c.1325T>C	p.Met442Thr	missense_variant	3/3	ENST00000254190.4	NP_055733.2	Q86X52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHSY1	ENST00000254190.4 linkuse as main transcript	c.1325T>C	p.Met442Thr	missense_variant	3/3	1	NM_014918.5	ENSP00000254190.3	Q86X52
CHSY1	ENST00000543813.2 linkuse as main transcript	n.*640T>C		non_coding_transcript_exon_variant	3/3	2		ENSP00000496160.1	A0A2R8Y7B7
CHSY1	ENST00000543813.2 linkuse as main transcript	n.*640T>C		3_prime_UTR_variant	3/3	2		ENSP00000496160.1	A0A2R8Y7B7

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

483

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00567

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00299

AC:

752

AN:

251488

Hom.:

AF XY:

0.00285

AC XY:

388

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.000694

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00526

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00605

AC:

8850

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00574

AC XY:

4171

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00277

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.000543

Gnomad4 NFE exome

AF:

0.00748

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.00317

AC:

483

AN:

152272

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00567

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00497

Hom.:

Bravo

AF:

0.00351

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00264

AC:

320

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 03, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 07, 2015	- -

Temtamy preaxial brachydactyly syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 14, 2021	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 05, 2020	Has not been previously published as pathogenic or benign to our knowledge -

CHSY1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 17, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.025

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.085

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

M_CAP

Benign

0.0064

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.9

REVEL

Benign

0.075

Sift

Benign

0.11

Sift4G

Benign

0.28

Polyphen

0.0010

Vest4

0.23

MVP

0.15

MPC

0.37

ClinPred

0.016

GERP RS

4.7

Varity_R

0.13

gMVP

0.60

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