NM_004984.4:c.820-19G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis, susceptibility to, 25
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), ClinGen
inherited neurodegenerative disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
myoclonus, intractable, neonatal
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
hereditary spastic paraplegia 10
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
autosomal dominant Charcot-Marie-Tooth disease type 2 due to KIF5A mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KIF5A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 382750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1111 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004984.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF5A	NM_004984.4	MANE Select	c.820-19G>T		intron	N/A	NP_004975.2
	KIF5A	NM_001354705.2		c.553-19G>T		intron	N/A	NP_001341634.1	J3KNA1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF5A	ENST00000455537.7	TSL:1 MANE Select	c.820-19G>T	intron	N/A	ENSP00000408979.2	Q12840
KIF5A	ENST00000674619.1		c.820-19G>T	intron	N/A	ENSP00000502270.1	A0A6Q8PGJ3
KIF5A	ENST00000938849.1		c.820-19G>T	intron	N/A	ENSP00000608908.1

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

GnomAD2 exomes

AF:

0.00789

AC:

1982

AN:

251304

AF XY:

0.00844

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 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

African (AFR)

AF:

0.00137

AC:

AN:

33474

American (AMR)

AF:

0.00300

AC:

134

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00287

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00753

AC:

649

AN:

86242

European-Finnish (FIN)

AF:

0.00802

AC:

428

AN:

53386

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0135

AC:

14955

AN:

1111548

Other (OTH)

AF:

0.00956

AC:

577

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

840

1679

2519

3358

4198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.00732

AC:

1111

AN:

151796

Hom.:

Cov.:

AF XY:

0.00709

AC XY:

526

AN XY:

74144

show subpopulations

African (AFR)

AF:

0.00174

AC:

AN:

41392

American (AMR)

AF:

0.00276

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5160

South Asian (SAS)

AF:

0.00605

AC:

AN:

4792

European-Finnish (FIN)

AF:

0.00904

AC:

AN:

10508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

854

AN:

67962

Other (OTH)

AF:

0.00428

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

109

163

218

272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

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:

0.00983

Hom.:

Bravo

AF:

0.00649

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Spastic paraplegia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.1

(source)

DANN

Benign

0.75

PhyloP100

-0.094

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over