3-134604035-G-A

Position:

• chr3-134604035-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_178554.6(KY):​c.1530C>T​(p.Arg510Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,614,012 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (23 hom., cov: 33)
  • Exomes 𝑓: 0.020 (348 hom.)
• Consequence: KY NM_178554.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.54

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-134604035-G-A is Benign according to our data. Variant chr3-134604035-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1300557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0148 (2260/152346) while in subpopulation NFE AF= 0.0234 (1591/68022). AF 95% confidence interval is 0.0224. There are 23 homozygotes in gnomad4. There are 1032 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KY	NM_178554.6	c.1530C>T	p.Arg510Arg	synonymous_variant	11/11	ENST00000423778.7	NP_848649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KY	ENST00000423778.7	c.1530C>T	p.Arg510Arg	synonymous_variant	11/11	5	NM_178554.6	ENSP00000397598.2

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152228 Hom.: 23 Cov.: 33

Gnomad AFR AF: 0.00475

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.0143 AC: 3569 AN: 248984 Hom.: 39 AF XY: 0.0140 AC XY: 1885 AN XY: 135064

Gnomad AFR exome AF: 0.00355

Gnomad AMR exome AF: 0.00597

Gnomad ASJ exome AF: 0.00487

Gnomad EAS exome AF: 0.000111

Gnomad SAS exome AF: 0.00101

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.0232

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0205 AC: 29900 AN: 1461666 Hom.: 348 Cov.: 70 AF XY: 0.0198 AC XY: 14406 AN XY: 727110

Gnomad4 AFR exome AF: 0.00311

Gnomad4 AMR exome AF: 0.00664

Gnomad4 ASJ exome AF: 0.00429

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000997

Gnomad4 FIN exome AF: 0.0268

Gnomad4 NFE exome AF: 0.0242

Gnomad4 OTH exome AF: 0.0155

GnomAD4 genome AF: 0.0148 AC: 2260 AN: 152346 Hom.: 23 Cov.: 33 AF XY: 0.0139 AC XY: 1032 AN XY: 74496

Gnomad4 AFR AF: 0.00474

Gnomad4 AMR AF: 0.00941

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0195 Hom.: 52

Bravo AF: 0.0136

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0200

EpiControl AF: 0.0209

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 02, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.7
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs35316983; hg19: chr3-134322877;