3-134603837-TCC-CCG

Variant names:

• chr3-134603837-TCC-CCG
• NM_178554.6:c.1726_1728delGGAinsCGG
• KY p.Gly576Arg

Variant summary

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

The NM_178554.6(KY):​c.1726_1728delGGAinsCGG​(p.Gly576Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KY NM_178554.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

Genes affected

KY (HGNC:26576): (kyphoscoliosis peptidase) The protein encoded by this gene belongs to the transglutaminase-like superfamily. The protein is involved in the function, maturation and stabilization of the neuromuscular junction and may be required for normal muscle growth. Mutations in this gene are associated with myopathy, myofibrillar, 7. [provided by RefSeq, Apr 2017]

ENSG00000288700 (HGNC:):

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

CEP63 Gene-Disease associations (from GenCC):

• Seckel syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178554.6. 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
	KY	NM_178554.6	MANE Select	c.1726_1728delGGAinsCGG	p.Gly576Arg	missense	N/A	NP_848649.3
	KY	NM_001350859.2		c.1678_1680delGGAinsCGG	p.Gly560Arg	missense	N/A	NP_001337788.1
	KY	NM_001366276.1		c.1663_1665delGGAinsCGG	p.Gly555Arg	missense	N/A	NP_001353205.1	Q8NBH2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KY	ENST00000423778.7	TSL:5 MANE Select	c.1726_1728delGGAinsCGG	p.Gly576Arg	missense	N/A	ENSP00000397598.2	Q8NBH2-4
	KY	ENST00000503669.1	TSL:1	c.*608_*610delGGAinsCGG		3_prime_UTR	Exon 10 of 10	ENSP00000426777.1	B4DGA7
	KY	ENST00000864999.1		c.1672_1674delGGAinsCGG	p.Gly558Arg	missense	N/A	ENSP00000535058.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-134322679;