3-134603672-T-C

Variant summary

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

The NM_178554.6(KY):ā€‹c.1893A>Gā€‹(p.Thr631Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00766 in 1,613,802 control chromosomes in the GnomAD database, including 849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.039 ( 421 hom., cov: 33)
Exomes š‘“: 0.0044 ( 428 hom. )

Consequence

KY
NM_178554.6 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -4.07
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 3-134603672-T-C is Benign according to our data. Variant chr3-134603672-T-C is described in ClinVar as [Benign]. Clinvar id is 1244064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.07 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KYNM_178554.6 linkuse as main transcriptc.1893A>G p.Thr631Thr synonymous_variant 11/11 ENST00000423778.7 NP_848649.3 Q8NBH2-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KYENST00000423778.7 linkuse as main transcriptc.1893A>G p.Thr631Thr synonymous_variant 11/115 NM_178554.6 ENSP00000397598.2 Q8NBH2-4

Frequencies

GnomAD3 genomes
AF:
0.0394
AC:
5994
AN:
152214
Hom.:
420
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.137
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0135
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000676
Gnomad OTH
AF:
0.0296
GnomAD3 exomes
AF:
0.0104
AC:
2578
AN:
249028
Hom.:
175
AF XY:
0.00771
AC XY:
1042
AN XY:
135078
show subpopulations
Gnomad AFR exome
AF:
0.144
Gnomad AMR exome
AF:
0.00714
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000443
Gnomad OTH exome
AF:
0.00662
GnomAD4 exome
AF:
0.00436
AC:
6365
AN:
1461470
Hom.:
428
Cov.:
30
AF XY:
0.00374
AC XY:
2717
AN XY:
726988
show subpopulations
Gnomad4 AFR exome
AF:
0.148
Gnomad4 AMR exome
AF:
0.00888
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000348
Gnomad4 OTH exome
AF:
0.00898
GnomAD4 genome
AF:
0.0394
AC:
6002
AN:
152332
Hom.:
421
Cov.:
33
AF XY:
0.0385
AC XY:
2869
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.137
Gnomad4 AMR
AF:
0.0135
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000827
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000676
Gnomad4 OTH
AF:
0.0293
Alfa
AF:
0.0174
Hom.:
88
Bravo
AF:
0.0447
Asia WGS
AF:
0.00722
AC:
25
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000593

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 29, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.14
DANN
Benign
0.54

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.

Other links and lift over

dbSNP: rs61745335; hg19: chr3-134322514; API