Genetic Variant KIF3A:c.1467-8A>T (chr5-132703073-T-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001300791.2(KIF3A):c.1467-8A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,597,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

KIF3A
NM_001300791.2 splice_region, intron

Scores

Splicing: ADA: 0.0001996

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.01

Publications

0 publications found

Variant links:

Genes affected

KIF3A (HGNC:6319): (kinesin family member 3A) Enables protein phosphatase binding activity; small GTPase binding activity; and spectrin binding activity. Involved in protein localization to cell junction and protein transport. Located in centriole and centrosome. Part of kinesin II complex. Colocalizes with spindle microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF3A links:

ENSG00000230612 (HGNC:):

ENSG00000230612 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 5-132703073-T-A is Benign according to our data. Variant chr5-132703073-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3057456.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 36 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300791.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF3A	NM_001300791.2	MANE Select	c.1467-8A>T	splice_region intron	N/A	NP_001287720.1	E9PES4
KIF3A	NM_001300792.2		c.1395-8A>T	splice_region intron	N/A	NP_001287721.1	J3KPF9
KIF3A	NM_007054.7		c.1386-8A>T	splice_region intron	N/A	NP_008985.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIF3A	ENST00000403231.6	TSL:2 MANE Select	c.1467-8A>T	splice_region intron	N/A	ENSP00000385808.1	E9PES4
KIF3A	ENST00000378735.5	TSL:1	c.1395-8A>T	splice_region intron	N/A	ENSP00000368009.1	J3KPF9
KIF3A	ENST00000618515.4	TSL:5	c.1464-8A>T	splice_region intron	N/A	ENSP00000483023.1	A0A087X011

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000282

AC:

AN:

237242

AF XY:

0.000249

show subpopulations

Gnomad AFR exome

AF:

0.000189

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000580

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000307

AC:

444

AN:

1445674

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

215

AN XY:

719580

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32572

American (AMR)

AF:

0.00

AC:

AN:

41166

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25862

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

83314

European-Finnish (FIN)

AF:

0.0000575

AC:

AN:

52154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000384

AC:

424

AN:

1105468

Other (OTH)

AF:

0.000267

AC:

AN:

59872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000237

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000485

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000423

Hom.:

Bravo

AF:

0.000264

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

KIF3A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.6

(source)

DANN

Benign

0.72

PhyloP100

2.0

PromoterAI

-0.0041

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00020

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.010

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