NM_014918.5:c.179_190delGGGCGCGCGGCG

Variant names:

• chr15-101251266-TCGCCGCGCGCCC-T
• rs1555437965
• NM_014918.5:c.179_190delGGGCGCGCGGCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_014918.5(CHSY1):​c.179_190delGGGCGCGCGGCG​(p.Gly60_Gly63del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000829 in 1,206,844 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: CHSY1 NM_014918.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.38
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_014918.5.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	NM_014918.5	MANE Select	c.179_190delGGGCGCGCGGCG	p.Gly60_Gly63del	disruptive_inframe_deletion	Exon 1 of 3	NP_055733.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHSY1	ENST00000254190.4	TSL:1 MANE Select	c.179_190delGGGCGCGCGGCG	p.Gly60_Gly63del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000254190.3
	CHSY1	ENST00000968149.1		c.179_190delGGGCGCGCGGCG	p.Gly60_Gly63del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000638208.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.29e-7 AC: 1 AN: 1206844 Hom.: 0 AF XY: 0.00000169 AC XY: 1 AN XY: 591620

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24372

American (AMR) AF: 0.00 AC: 0 AN: 15690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18592

East Asian (EAS) AF: 0.00 AC: 0 AN: 26458

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 51972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4604

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 987876

Other (OTH) AF: 0.00 AC: 0 AN: 48354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1555437965; hg19: chr15-101791471;