12-57549925-A-G
Variant names:
Variant summary
Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The ENST00000676250.1(KIF5A):c.-25+3613A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 303,026 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0086 ( 21 hom., cov: 31)
Exomes 𝑓: 0.00030 ( 0 hom. )
Consequence
KIF5A
ENST00000676250.1 intron
ENST00000676250.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.508
Publications
1 publications found
Genes affected
KIF5A (HGNC:6323): (kinesin family member 5A) This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multisubunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10. [provided by RefSeq, Jul 2008]
KIF5A Gene-Disease associations (from GenCC):
- amyotrophic lateral sclerosis, susceptibility to, 25Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
- inherited neurodegenerative disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- myoclonus, intractable, neonatalInheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
- hereditary spastic paraplegia 10Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 12-57549925-A-G is Benign according to our data. Variant chr12-57549925-A-G is described in CliVar as Likely_benign. Clinvar id is 1201242.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00865 (1313/151806) while in subpopulation AFR AF = 0.0302 (1253/41422). AF 95% confidence interval is 0.0289. There are 21 homozygotes in GnomAd4. There are 624 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High AC in GnomAd4 at 1313 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00863 AC: 1309AN: 151698Hom.: 21 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1309
AN:
151698
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000298 AC: 45AN: 151220Hom.: 0 AF XY: 0.000230 AC XY: 19AN XY: 82524 show subpopulations
GnomAD4 exome
AF:
AC:
45
AN:
151220
Hom.:
AF XY:
AC XY:
19
AN XY:
82524
show subpopulations
African (AFR)
AF:
AC:
30
AN:
1408
American (AMR)
AF:
AC:
6
AN:
4658
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3308
East Asian (EAS)
AF:
AC:
0
AN:
3922
South Asian (SAS)
AF:
AC:
3
AN:
28912
European-Finnish (FIN)
AF:
AC:
0
AN:
9064
Middle Eastern (MID)
AF:
AC:
1
AN:
550
European-Non Finnish (NFE)
AF:
AC:
0
AN:
91572
Other (OTH)
AF:
AC:
5
AN:
7826
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.514
Heterozygous variant carriers
0
3
6
8
11
14
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.00865 AC: 1313AN: 151806Hom.: 21 Cov.: 31 AF XY: 0.00841 AC XY: 624AN XY: 74192 show subpopulations
GnomAD4 genome
AF:
AC:
1313
AN:
151806
Hom.:
Cov.:
31
AF XY:
AC XY:
624
AN XY:
74192
show subpopulations
African (AFR)
AF:
AC:
1253
AN:
41422
American (AMR)
AF:
AC:
46
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5146
South Asian (SAS)
AF:
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
AC:
0
AN:
10582
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
4
AN:
67802
Other (OTH)
AF:
AC:
10
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
65
130
196
261
326
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
7
AN:
3476
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Sep 08, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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