3-134603321-C-A

Position:

• chr3-134603321-C-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.21

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:):

ACMG classification

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/exons	MANE	Protein	UniProt
KY	NM_178554.6	c.*258G>T		3_prime_UTR_variant	11/11	ENST00000423778.7	NP_848649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KY	ENST00000423778	c.*258G>T		3_prime_UTR_variant	11/11	5	NM_178554.6	ENSP00000397598.2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95812 AN: 152028 Hom.: 30691 Cov.: 33

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.: 2 AF XY: 0.650 AC XY: 79533 AN XY: 122354

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.: 33 AF XY: 0.638 AC XY: 47440 AN XY: 74380

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 06, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
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

Other links and lift over

dbSNP: rs1880375; hg19: chr3-134322163;