chr15-101178745-T-C

Variant names:

• chr15-101178745-T-C
• rs74752435
• NM_014918.5:c.1052A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014918.5(CHSY1):​c.1052A>G​(p.Lys351Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,614,188 control chromosomes in the GnomAD database, including 358 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (35 hom., cov: 33)
  • Exomes 𝑓: 0.016 (323 hom.)
• Consequence: CHSY1 NM_014918.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.31
• Publications: 9 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014885366).
• BP6: Variant 15-101178745-T-C is Benign according to our data. Variant chr15-101178745-T-C is described in ClinVar as Benign. ClinVar VariationId is 466168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	NM_014918.5	MANE Select	c.1052A>G	p.Lys351Arg	missense	Exon 3 of 3	NP_055733.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.1052A>G	p.Lys351Arg	missense	Exon 3 of 3	ENSP00000254190.3
	CHSY1	ENST00000543813.2	TSL:2	n.*367A>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000496160.1
	CHSY1	ENST00000560766.1	TSL:4	n.385A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2508 AN: 152192 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.00591

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0758

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.0250 AC: 6286 AN: 251486 AF XY: 0.0231

Gnomad AFR exome AF: 0.00418

Gnomad AMR exome AF: 0.0558

Gnomad ASJ exome AF: 0.0317

Gnomad EAS exome AF: 0.0798

Gnomad FIN exome AF: 0.0276

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.0235

GnomAD4 exome AF: 0.0156 AC: 22736 AN: 1461878 Hom.: 323 Cov.: 35 AF XY: 0.0152 AC XY: 11071 AN XY: 727238

African (AFR) AF: 0.00418 AC: 140 AN: 33480

American (AMR) AF: 0.0547 AC: 2445 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 806 AN: 26136

East Asian (EAS) AF: 0.0650 AC: 2580 AN: 39700

South Asian (SAS) AF: 0.0125 AC: 1076 AN: 86256

European-Finnish (FIN) AF: 0.0274 AC: 1462 AN: 53420

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5768

European-Non Finnish (NFE) AF: 0.0117 AC: 13034 AN: 1111998

Other (OTH) AF: 0.0187 AC: 1128 AN: 60396

GnomAD4 genome AF: 0.0165 AC: 2513 AN: 152310 Hom.: 35 Cov.: 33 AF XY: 0.0176 AC XY: 1311 AN XY: 74490

African (AFR) AF: 0.00599 AC: 249 AN: 41568

American (AMR) AF: 0.0354 AC: 542 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.0756 AC: 392 AN: 5186

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4824

European-Finnish (FIN) AF: 0.0265 AC: 281 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0123 AC: 837 AN: 68020

Other (OTH) AF: 0.0175 AC: 37 AN: 2110

Alfa AF: 0.0151 Hom.: 104

Bravo AF: 0.0172

TwinsUK AF: 0.0111 AC: 41

ALSPAC AF: 0.0112 AC: 43

ESP6500AA AF: 0.00340 AC: 15

ESP6500EA AF: 0.0116 AC: 100

ExAC AF: 0.0215 AC: 2611

Asia WGS AF: 0.0370 AC: 128 AN: 3478

EpiCase AF: 0.0131

EpiControl AF: 0.0113

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 08, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Oct 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Temtamy preaxial brachydactyly syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.52	N
PhyloP100		2.3
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.047
Sift	Benign	0.40	T
Sift4G	Benign	0.57	T
Polyphen		0.0030	B
Vest4		0.024
MPC		0.26
ClinPred		0.0038	T
GERP RS		4.5
Varity_R		0.036
gMVP		0.28
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs74752435; hg19: chr15-101718950; COSMIC: COSV54251976;