15-101177683-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014918.5(CHSY1):c.2114G>A(p.Arg705Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,614,080 control chromosomes in the GnomAD database, including 14,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1082 hom., cov: 33)
  • Exomes 𝑓: 0.13 (13621 hom.)
• Consequence: CHSY1 NM_014918.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.74

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016215444).
• BP6: Variant 15-101177683-C-T is Benign according to our data. Variant chr15-101177683-C-T is described in ClinVar as [Benign]. Clinvar id is 1167689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHSY1	NM_014918.5	c.2114G>A	p.Arg705Gln	missense_variant	3/3	ENST00000254190.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHSY1	ENST00000254190.4	c.2114G>A	p.Arg705Gln	missense_variant	3/3	1	NM_014918.5	P1
CHSY1	ENST00000543813.2	c.*1429G>A		3_prime_UTR_variant, NMD_transcript_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15333 AN: 152090 Hom.: 1083 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0803

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0631

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.101

GnomAD3 exomes AF: 0.107 AC: 26847 AN: 251454 Hom.: 1782 AF XY: 0.109 AC XY: 14827 AN XY: 135906

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.0651

Gnomad ASJ exome AF: 0.156

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.0686

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.142

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.131 AC: 190848 AN: 1461872 Hom.: 13621 Cov.: 67 AF XY: 0.129 AC XY: 93834 AN XY: 727236

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.0663

Gnomad4 ASJ exome AF: 0.153

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0689

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.101 AC: 15330 AN: 152208 Hom.: 1082 Cov.: 33 AF XY: 0.101 AC XY: 7522 AN XY: 74412

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0629

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.100

Alfa AF: 0.129 Hom.: 2204

Bravo AF: 0.0893

TwinsUK AF: 0.156 AC: 577

ALSPAC AF: 0.144 AC: 556

ESP6500AA AF: 0.0275 AC: 121

ESP6500EA AF: 0.142 AC: 1221

ExAC AF: 0.105 AC: 12797

Asia WGS AF: 0.0300 AC: 105 AN: 3478

EpiCase AF: 0.144

EpiControl AF: 0.139

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Temtamy preaxial brachydactyly syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	19
Dann	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	0.0023
Eigen_PC	Benign	0.095
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
MutationTaster	Benign	0.00023	P
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.051
Sift	Benign	0.55	T
Sift4G	Benign	0.51	T
Polyphen		0.90	P
Vest4		0.042
MPC		0.37
ClinPred		0.013	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.063
gMVP		0.45

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

Other links and lift over

dbSNP: rs62621399; hg19: chr15-101717888; COSMIC: COSV54255154; COSMIC: COSV54255154;