Variant chr12-57564530-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004984.4(KIF5A):c.445+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,577,814 control chromosomes in the GnomAD database, including 137,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14309 hom., cov: 32)

Exomes 𝑓: 0.40 ( 123638 hom. )

Consequence

KIF5A
NM_004984.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0400

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]

KIF5A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 12-57564530-A-G is Benign according to our data. Variant chr12-57564530-A-G is described in ClinVar as [Benign]. Clinvar id is 682854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF5A	NM_004984.4 linkuse as main transcript	c.445+22A>G		intron_variant		ENST00000455537.7
KIF5A	NM_001354705.2 linkuse as main transcript	c.178+22A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
KIF5A	ENST00000455537.7 linkuse as main transcript	c.445+22A>G	intron_variant	1	NM_004984.4	P1
KIF5A	ENST00000286452.5 linkuse as main transcript	c.178+22A>G	intron_variant	2
KIF5A	ENST00000674619.1 linkuse as main transcript	c.445+22A>G	intron_variant
KIF5A	ENST00000676457.1 linkuse as main transcript	c.340+22A>G	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64539

AN:

151884

Hom.:

14270

Cov.:

show subpopulations

Gnomad AFR

AF:

0.422

Gnomad AMI

AF:

0.511

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.605

Gnomad FIN

AF:

0.538

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.395

GnomAD3 exomes

AF:

0.469

AC:

117745

AN:

251074

Hom.:

29659

AF XY:

0.469

AC XY:

63632

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.518

Gnomad ASJ exome

AF:

0.369

Gnomad EAS exome

AF:

0.787

Gnomad SAS exome

AF:

0.592

Gnomad FIN exome

AF:

0.534

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.403

AC:

575124

AN:

1425812

Hom.:

123638

Cov.:

AF XY:

0.408

AC XY:

290600

AN XY:

711536

show subpopulations

Gnomad4 AFR exome

AF:

0.417

Gnomad4 AMR exome

AF:

0.508

Gnomad4 ASJ exome

AF:

0.374

Gnomad4 EAS exome

AF:

0.788

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.519

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.425

AC:

64632

AN:

152002

Hom.:

14309

Cov.:

AF XY:

0.437

AC XY:

32493

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.368

Gnomad4 EAS

AF:

0.771

Gnomad4 SAS

AF:

0.605

Gnomad4 FIN

AF:

0.538

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.378

Hom.:

11644

Bravo

AF:

0.418

Asia WGS

AF:

0.658

AC:

2285

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Myoclonus, intractable, neonatal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Hereditary spastic paraplegia 10

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

-0.91

CADD

Benign

1.5

DANN

Benign

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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