rs537608637

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001244008.2(KIF1A):c.2751G>T(p.Glu917Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000042 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIF1A
NM_001244008.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

6 publications found

Variant links:

Genes affected

KIF1A (HGNC:888): (kinesin family member 1A) The protein encoded by this gene is a member of the kinesin family and functions as an anterograde motor protein that transports membranous organelles along axonal microtubules. Mutations at this locus have been associated with spastic paraplegia-30 and hereditary sensory neuropathy IIC. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Apr 2012]

KIF1A Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 9
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
syndromic intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
neuropathy, hereditary sensory, type 2C
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
hereditary spastic paraplegia 30
Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
PEHO syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary sensory and autonomic neuropathy type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054769307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF1A	NM_001244008.2 link	c.2751G>T	p.Glu917Asp	missense_variant	Exon 27 of 49	ENST00000498729.9	NP_001230937.1	Q12756-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF1A	ENST00000498729.9 link	c.2751G>T	p.Glu917Asp	missense_variant	Exon 27 of 49	5	NM_001244008.2	ENSP00000438388.1		Q12756-3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

22392

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000421

AC:

AN:

213702

Hom.:

Cov.:

AF XY:

0.0000664

AC XY:

AN XY:

105394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

578

American (AMR)

AF:

0.00

AC:

AN:

7182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2342

East Asian (EAS)

AF:

0.00

AC:

AN:

2118

South Asian (SAS)

AF:

0.0000594

AC:

AN:

16840

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

880

European-Non Finnish (NFE)

AF:

0.0000413

AC:

AN:

169680

Other (OTH)

AF:

0.000129

AC:

AN:

7750

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

22392

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

11324

African (AFR)

AF:

0.00

AC:

AN:

830

American (AMR)

AF:

0.00

AC:

AN:

3300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

474

East Asian (EAS)

AF:

0.00

AC:

AN:

454

South Asian (SAS)

AF:

0.00

AC:

AN:

1592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2372

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

12962

Other (OTH)

AF:

0.00

AC:

AN:

276

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

May 25, 2022

GeneDx

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Located in an alternate transcript of the gene; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.40

T;.;T;T

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.055

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

1.4

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.47

N;.;.;N

REVEL

Benign

0.091

Sift

Benign

0.44

T;.;.;T

Sift4G

Benign

0.65

T;.;.;.

Polyphen

0.0

.;.;.;B

Vest4

0.19

MutPred

0.16

Loss of helix (P = 0.1299);.;.;Loss of helix (P = 0.1299);

MVP

0.35

MPC

0.39

ClinPred

0.10

GERP RS

3.2

gMVP

0.47

Mutation Taster

=96/4

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over