15-101251400-G-T

Variant names:

• chr15-101251400-G-T
• rs7175303
• NM_014918.5:c.57C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014918.5(CHSY1):​c.57C>A​(p.Gly19Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000984 in 1,016,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G19G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 9.8e-7 (0 hom.)
• Consequence: CHSY1 NM_014918.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.108 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHSY1	NM_014918.5	c.57C>A	p.Gly19Gly	synonymous_variant	Exon 1 of 3	ENST00000254190.4	NP_055733.2
CHSY1	XM_011521364.3	c.57C>A	p.Gly19Gly	synonymous_variant	Exon 1 of 4		XP_011519666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHSY1	ENST00000254190.4	c.57C>A	p.Gly19Gly	synonymous_variant	Exon 1 of 3	1	NM_014918.5	ENSP00000254190.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.84e-7 AC: 1 AN: 1016376 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 497644

African (AFR) AF: 0.00 AC: 0 AN: 19462

American (AMR) AF: 0.00 AC: 0 AN: 17298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12698

East Asian (EAS) AF: 0.00 AC: 0 AN: 5460

South Asian (SAS) AF: 0.00 AC: 0 AN: 57122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2314

European-Non Finnish (NFE) AF: 0.00000117 AC: 1 AN: 858046

Other (OTH) AF: 0.00 AC: 0 AN: 35002

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs7175303; hg19: chr15-101791605;