rs587780375

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198525.3(KIF7):c.1220C>T(p.Ala407Val) variant causes a missense change. The variant allele was found at a frequency of 0.000045 in 1,044,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A407D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

KIF7
NM_198525.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.84

Publications

2 publications found

Variant links:

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

KIF7 Gene-Disease associations (from GenCC):

acrocallosal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hydrolethalus syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
hydrolethalus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
multiple epiphyseal dysplasia, Al-Gazali type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15037793).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198525.3. 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
	KIF7	NM_198525.3	MANE Select	c.1220C>T	p.Ala407Val	missense	Exon 5 of 19	NP_940927.2	Q2M1P5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF7	ENST00000394412.8	TSL:5 MANE Select	c.1220C>T	p.Ala407Val	missense	Exon 5 of 19	ENSP00000377934.3	Q2M1P5
KIF7	ENST00000696512.1		c.1343C>T	p.Ala448Val	missense	Exon 5 of 19	ENSP00000512678.1	A0A8Q3SIQ8
KIF7	ENST00000946200.1		c.1220C>T	p.Ala407Val	missense	Exon 5 of 19	ENSP00000616259.1

Frequencies

GnomAD3 genomes

AF:

0.0000273

AC:

AN:

146564

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000678

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:

0.0000455

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

898154

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

419684

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16710

American (AMR)

AF:

0.00

AC:

AN:

2766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6692

East Asian (EAS)

AF:

0.00

AC:

AN:

8910

South Asian (SAS)

AF:

0.00

AC:

AN:

17936

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10198

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1904

European-Non Finnish (NFE)

AF:

0.0000536

AC:

AN:

802104

Other (OTH)

AF:

0.00

AC:

AN:

30934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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

AF:

0.0000273

AC:

AN:

146564

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71292

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40906

American (AMR)

AF:

0.0000678

AC:

AN:

14754

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3394

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000455

AC:

AN:

65940

Other (OTH)

AF:

0.00

AC:

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.73

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.46

PhyloP100

3.8

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.3

REVEL

Benign

0.072

Sift

Benign

0.31

Sift4G

Benign

0.39

Polyphen

0.010

Vest4

0.087

MutPred

0.33

Gain of helix (P = 0.027)

MVP

0.70

MPC

0.020

ClinPred

0.71

GERP RS

3.9

Varity_R

0.14

gMVP

0.53

Mutation Taster

=26/74

disease causing

(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