Variant 3-134603972-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_178554.6(KY):c.1593C>G(p.Gly531Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,613,574 control chromosomes in the GnomAD database, including 99,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9909 hom., cov: 33)

Exomes 𝑓: 0.35 ( 89407 hom. )

Consequence

KY
NM_178554.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.956

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 3-134603972-G-C is Benign according to our data. Variant chr3-134603972-G-C is described in ClinVar as [Benign]. Clinvar id is 1251525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.956 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KY	NM_178554.6 linkuse as main transcript	c.1593C>G	p.Gly531Gly	synonymous_variant	11/11	ENST00000423778.7	NP_848649.3	Q8NBH2-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KY	ENST00000423778.7 linkuse as main transcript	c.1593C>G	p.Gly531Gly	synonymous_variant	11/11	5	NM_178554.6	ENSP00000397598.2		Q8NBH2-4

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53710

AN:

151998

Hom.:

9899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.417

Gnomad AMI

AF:

0.527

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.314

AC:

78114

AN:

249012

Hom.:

13277

AF XY:

0.324

AC XY:

43756

AN XY:

135094

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.395

Gnomad EAS exome

AF:

0.115

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.321

GnomAD4 exome

AF:

0.345

AC:

504411

AN:

1461458

Hom.:

89407

Cov.:

AF XY:

0.347

AC XY:

252364

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.186

Gnomad4 ASJ exome

AF:

0.392

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.379

Gnomad4 FIN exome

AF:

0.275

Gnomad4 NFE exome

AF:

0.357

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.353

AC:

53751

AN:

152116

Hom.:

9909

Cov.:

AF XY:

0.346

AC XY:

25720

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.417

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.361

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.358

Gnomad4 OTH

AF:

0.359

Alfa

AF:

0.354

Hom.:

3129

Bravo

AF:

0.353

Asia WGS

AF:

0.253

AC:

879

AN:

3476

EpiCase

AF:

0.359

EpiControl

AF:

0.360

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Myofibrillar myopathy 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.75

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