rs181688415

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004984.4(KIF5A):c.820-19G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,140 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 7 hom., cov: 32)

Exomes 𝑓: 0.012 ( 126 hom. )

Consequence

KIF5A
NM_004984.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.0940

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=-0.72).

BP6

Variant 12-57569237-G-T is Benign according to our data. Variant chr12-57569237-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 382750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57569237-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00732 (1111/151796) while in subpopulation NFE AF= 0.0126 (854/67962). AF 95% confidence interval is 0.0119. There are 7 homozygotes in gnomad4. There are 526 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF5A	NM_004984.4 link	c.820-19G>T		intron_variant	Intron 9 of 28	ENST00000455537.7	NP_004975.2	Q12840
KIF5A	NM_001354705.2 link	c.553-19G>T		intron_variant	Intron 6 of 25		NP_001341634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF5A	ENST00000455537.7 link	c.820-19G>T		intron_variant	Intron 9 of 28	1	NM_004984.4	ENSP00000408979.2		Q12840

Frequencies

GnomAD3 genomes

AF:

0.00732

AC:

1111

AN:

151678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00277

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00605

Gnomad FIN

AF:

0.00904

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.00789

AC:

1982

AN:

251304

Hom.:

AF XY:

0.00844

AC XY:

1146

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00258

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00683

Gnomad FIN exome

AF:

0.00767

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.0115

AC:

16876

AN:

1461344

Hom.:

126

Cov.:

AF XY:

0.0116

AC XY:

8416

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.00137

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00753

Gnomad4 FIN exome

AF:

0.00802

Gnomad4 NFE exome

AF:

0.0135

Gnomad4 OTH exome

AF:

0.00956

GnomAD4 genome

AF:

0.00732

AC:

1111

AN:

151796

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

526

AN XY:

74144

show subpopulations

Gnomad4 AFR

AF:

0.00174

Gnomad4 AMR

AF:

0.00276

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00605

Gnomad4 FIN

AF:

0.00904

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00428

Alfa

AF:

0.00983

Hom.:

Bravo

AF:

0.00649

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 30, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 18, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jan 30, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Spastic paraplegia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.1

DANN

Benign

0.75

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