3-134603375-C-G

Variant names:

• chr3-134603375-C-G
• rs6800742
• NM_178554.6:c.*204G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178554.6(KY):​c.*204G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 502,820 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (4 hom.)
• Consequence: KY NM_178554.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.95
• 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 3-134603375-C-G is Benign according to our data. Variant chr3-134603375-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1683805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00633 (965/152332) while in subpopulation AFR AF = 0.0223 (927/41578). AF 95% confidence interval is 0.0211. There are 6 homozygotes in GnomAd4. There are 437 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

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.*204G>C		3_prime_UTR	Exon 11 of 11	NP_848649.3
	KY	NM_001350859.2		c.*204G>C		3_prime_UTR	Exon 10 of 10	NP_001337788.1
	KY	NM_001366276.1		c.*204G>C		3_prime_UTR	Exon 10 of 10	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.*204G>C		3_prime_UTR	Exon 11 of 11	ENSP00000397598.2	Q8NBH2-4
	KY	ENST00000864999.1		c.*204G>C		3_prime_UTR	Exon 11 of 11	ENSP00000535058.1
	KY	ENST00000508956.5	TSL:2	c.*204G>C		3_prime_UTR	Exon 10 of 10	ENSP00000421297.1	Q8NBH2-3

Frequencies

GnomAD3 genomes AF: 0.00631 AC: 961 AN: 152214 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0223

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000956 AC: 335 AN: 350488 Hom.: 4 Cov.: 4 AF XY: 0.000815 AC XY: 148 AN XY: 181574

African (AFR) AF: 0.0262 AC: 269 AN: 10268

American (AMR) AF: 0.00179 AC: 21 AN: 11760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11230

East Asian (EAS) AF: 0.00 AC: 0 AN: 26984

South Asian (SAS) AF: 0.0000469 AC: 1 AN: 21340

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27116

Middle Eastern (MID) AF: 0.00121 AC: 2 AN: 1656

European-Non Finnish (NFE) AF: 0.0000137 AC: 3 AN: 218594

Other (OTH) AF: 0.00181 AC: 39 AN: 21540

GnomAD4 genome AF: 0.00633 AC: 965 AN: 152332 Hom.: 6 Cov.: 33 AF XY: 0.00587 AC XY: 437 AN XY: 74488

African (AFR) AF: 0.0223 AC: 927 AN: 41578

American (AMR) AF: 0.00144 AC: 22 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00576 Hom.: 2

Bravo AF: 0.00728

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.5
DANN	Benign	0.61
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism

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: rs6800742; hg19: chr3-134322217;