Variant 3-134603900-A-G 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.1665T>C(p.Leu555Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 1,613,692 control chromosomes in the GnomAD database, including 343,051 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.63 ( 30750 hom., cov: 33)

Exomes 𝑓: 0.65 ( 312301 hom. )

Consequence

KY
NM_178554.6 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.423

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=-0.87).

BP6

Variant 3-134603900-A-G is Benign according to our data. Variant chr3-134603900-A-G is described in ClinVar as [Benign]. Clinvar id is 1289017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.423 with no splicing effect.

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 linkuse as main transcript	c.1665T>C	p.Leu555Leu	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.1665T>C	p.Leu555Leu	synonymous_variant	11/11	5	NM_178554.6	ENSP00000397598.2		Q8NBH2-4

Frequencies

GnomAD3 genomes

AF:

0.631

AC:

95865

AN:

151962

Hom.:

30734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.534

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.714

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:

0.641

Gnomad OTH

AF:

0.628

GnomAD3 exomes

AF:

0.681

AC:

169566

AN:

249096

Hom.:

58872

AF XY:

0.671

AC XY:

90685

AN XY:

135140

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.819

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.884

Gnomad SAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.732

Gnomad NFE exome

AF:

0.644

Gnomad OTH exome

AF:

0.674

GnomAD4 exome

AF:

0.651

AC:

951734

AN:

1461610

Hom.:

312301

Cov.:

AF XY:

0.649

AC XY:

471981

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.809

Gnomad4 ASJ exome

AF:

0.605

Gnomad4 EAS exome

AF:

0.836

Gnomad4 SAS exome

AF:

0.613

Gnomad4 FIN exome

AF:

0.725

Gnomad4 NFE exome

AF:

0.642

Gnomad4 OTH exome

AF:

0.655

GnomAD4 genome

AF:

0.631

AC:

95921

AN:

152082

Hom.:

30750

Cov.:

AF XY:

0.639

AC XY:

47491

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.534

Gnomad4 AMR

AF:

0.715

Gnomad4 ASJ

AF:

0.607

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.631

Gnomad4 FIN

AF:

0.730

Gnomad4 NFE

AF:

0.641

Gnomad4 OTH

AF:

0.629

Alfa

AF:

0.646

Hom.:

38767

Bravo

AF:

0.629

Asia WGS

AF:

0.721

AC:

2507

AN:

3478

EpiCase

AF:

0.639

EpiControl

AF:

0.639

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

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

-0.87

CADD

Benign

2.3

DANN

Benign

0.73

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