Genetic Variant KY:c.*258G>T (chr3-134603321-C-A) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_178554.6(KY):c.*258G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 393,332 control chromosomes in the GnomAD database, including 83,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30705 hom., cov: 33)

Exomes 𝑓: 0.65 ( 52398 hom. )

Consequence

KY
NM_178554.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.21

Variant links:

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]

KY links:

ENSG00000288700 (HGNC:):

ENSG00000288700 links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 3-134603321-C-A is Benign according to our data. Variant chr3-134603321-C-A is described in ClinVar as [Benign]. Clinvar id is 1287230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KY	NM_178554.6 link	c.*258G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000423778.7	NP_848649.3	Q8NBH2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KY	ENST00000423778 link	c.*258G>T		3_prime_UTR_variant	Exon 11 of 11	5	NM_178554.6	ENSP00000397598.2		Q8NBH2-4

Frequencies

GnomAD3 genomes

AF:

0.630

AC:

95812

AN:

152028

Hom.:

30691

Cov.:

show subpopulations

Gnomad AFR

AF:

0.533

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.713

Gnomad ASJ

AF:

0.607

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.630

Gnomad FIN

AF:

0.730

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.640

Gnomad OTH

AF:

0.627

GnomAD4 exome

AF:

0.652

AC:

157348

AN:

241186

Hom.:

52398

Cov.:

AF XY:

0.650

AC XY:

79533

AN XY:

122354

show subpopulations

Gnomad4 AFR exome

AF:

0.519

Gnomad4 AMR exome

AF:

0.752

Gnomad4 ASJ exome

AF:

0.600

Gnomad4 EAS exome

AF:

0.812

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.713

Gnomad4 NFE exome

AF:

0.635

Gnomad4 OTH exome

AF:

0.650

GnomAD4 genome

AF:

0.630

AC:

95864

AN:

152146

Hom.:

30705

Cov.:

AF XY:

0.638

AC XY:

47440

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.533

Gnomad4 AMR

AF:

0.714

Gnomad4 ASJ

AF:

0.607

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.631

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.640

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.638

Hom.:

6382

Bravo

AF:

0.629

Asia WGS

AF:

0.720

AC:

2504

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 06, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over