rs145062338

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BS1BS2

The ENST00000455537.7(KIF5A):​c.2412C>T​(p.Asp804=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 1,614,000 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 3 hom. )

Consequence

KIF5A
ENST00000455537.7 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.42
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.17).
BP6
Variant 12-57578059-C-T is Benign according to our data. Variant chr12-57578059-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 240086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.42 with no splicing effect.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000452 (661/1461790) while in subpopulation MID AF= 0.00225 (13/5768). AF 95% confidence interval is 0.00133. There are 3 homozygotes in gnomad4_exome. There are 334 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 56 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF5ANM_004984.4 linkuse as main transcriptc.2412C>T p.Asp804= synonymous_variant 22/29 ENST00000455537.7 NP_004975.2
KIF5ANM_001354705.2 linkuse as main transcriptc.2145C>T p.Asp715= synonymous_variant 19/26 NP_001341634.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF5AENST00000455537.7 linkuse as main transcriptc.2412C>T p.Asp804= synonymous_variant 22/291 NM_004984.4 ENSP00000408979 P1

Frequencies

GnomAD3 genomes
AF:
0.000368
AC:
56
AN:
152210
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00893
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000521
AC:
131
AN:
251474
Hom.:
1
AF XY:
0.000515
AC XY:
70
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00794
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000316
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000452
AC:
661
AN:
1461790
Hom.:
3
Cov.:
31
AF XY:
0.000459
AC XY:
334
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00800
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000383
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000288
Gnomad4 OTH exome
AF:
0.00137
GnomAD4 genome
AF:
0.000368
AC:
56
AN:
152210
Hom.:
0
Cov.:
32
AF XY:
0.000350
AC XY:
26
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00893
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000323
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000981
Hom.:
1
Bravo
AF:
0.000378
EpiCase
AF:
0.000818
EpiControl
AF:
0.000711

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024KIF5A: BP4, BS2 -
Benign, criteria provided, single submitterclinical testingGeneDxMay 14, 2019- -
Spastic paraplegia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Aug 09, 2017- -
Hereditary spastic paraplegia 10 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, The Hospital for Sick ChildrenApr 01, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.17
CADD
Benign
15
DANN
Benign
0.65

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: rs145062338; hg19: chr12-57971842; API