3-134604015-C-G

Variant names:

• chr3-134604015-C-G
• NM_178554.6:c.1550G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178554.6(KY):​c.1550G>C​(p.Arg517Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R517Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KY NM_178554.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KY	NM_178554.6	c.1550G>C	p.Arg517Pro	missense_variant	Exon 11 of 11	ENST00000423778.7	NP_848649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KY	ENST00000423778.7	c.1550G>C	p.Arg517Pro	missense_variant	Exon 11 of 11	5	NM_178554.6	ENSP00000397598.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461632 Hom.: 0 Cov.: 69 AF XY: 0.00000138 AC XY: 1 AN XY: 727098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.16
Sift	Benign	0.23	T;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.99	D;D
Vest4		0.60
MutPred		0.38		Gain of loop (P = 0.0079);.;
MVP		0.68
MPC		0.73
ClinPred		0.94	D
GERP RS		5.6
gMVP		0.84

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-134322857;