dbSNP rs3756754: KIF3A:c.-368C>T (chr5-132737787-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001300791.2(KIF3A):c.-368C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00173 in 386,054 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00092 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 12 hom. )

Consequence

KIF3A
NM_001300791.2 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.520

Publications

1 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000919 (140/152390) while in subpopulation EAS AF = 0.0254 (132/5192). AF 95% confidence interval is 0.0219. There are 1 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 140 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
KIF3A	NM_001300791.2	MANE Select	c.-368C>T	upstream_gene	N/A	NP_001287720.1
KIF3A	NM_001300792.2		c.-368C>T	upstream_gene	N/A	NP_001287721.1
KIF3A	NM_007054.7		c.-368C>T	upstream_gene	N/A	NP_008985.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KIF3A	ENST00000403231.6	TSL:2 MANE Select	c.-368C>T	upstream_gene	N/A	ENSP00000385808.1
KIF3A	ENST00000378735.5	TSL:1	c.-368C>T	upstream_gene	N/A	ENSP00000368009.1
KIF3A	ENST00000618515.4	TSL:5	c.-368C>T	upstream_gene	N/A	ENSP00000483023.1

Frequencies

GnomAD3 genomes

AF:

0.000926

AC:

141

AN:

152272

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0254

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD4 exome

AF:

0.00226

AC:

529

AN:

233664

Hom.:

AF XY:

0.00200

AC XY:

239

AN XY:

119368

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6494

American (AMR)

AF:

0.00

AC:

AN:

6440

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8676

East Asian (EAS)

AF:

0.0264

AC:

504

AN:

19122

South Asian (SAS)

AF:

0.000243

AC:

AN:

8222

European-Finnish (FIN)

AF:

0.000103

AC:

AN:

19384

Middle Eastern (MID)

AF:

0.000845

AC:

AN:

1184

European-Non Finnish (NFE)

AF:

0.0000471

AC:

AN:

148642

Other (OTH)

AF:

0.000839

AC:

AN:

15500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.000919

AC:

140

AN:

152390

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41594

American (AMR)

AF:

0.0000653

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0254

AC:

132

AN:

5192

South Asian (SAS)

AF:

0.000828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68038

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000277

Hom.:

Bravo

AF:

0.00130

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.2

(source)

DANN

Benign

0.74

PhyloP100

-0.52

PromoterAI

-0.13

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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