13-101714524-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004791.3(ITGBL1):c.1366G>A(p.Asp456Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,607,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Publications

2 publications found

Variant links:

Genes affected

ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ITGBL1 links:

FGF14 (HGNC:3671): (fibroblast growth factor 14) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

FGF14 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 27A
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
spinocerebellar ataxia type 27
Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
autosomal recessive cerebellar ataxia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

FGF14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3 link	c.1366G>A	p.Asp456Asn	missense_variant	Exon 10 of 11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
FGF14	NM_004115.4 link	c.*8307C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000376143.5	NP_004106.1	Q92915-1A0A7U3JVZ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8 link	c.1366G>A	p.Asp456Asn	missense_variant	Exon 10 of 11	1	NM_004791.3	ENSP00000365351.3		O95965-1
FGF14	ENST00000376143.5 link	c.*8307C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_004115.4	ENSP00000365313.4		Q92915-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251406

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1454980

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724378

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33312

American (AMR)

AF:

0.0000447

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39650

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86074

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000633

AC:

AN:

1105794

Other (OTH)

AF:

0.0000166

AC:

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41420

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 29, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1366G>A (p.D456N) alteration is located in exon 10 (coding exon 10) of the ITGBL1 gene. This alteration results from a G to A substitution at nucleotide position 1366, causing the aspartic acid (D) at amino acid position 456 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.024

T;T;T;.;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Uncertain

0.086

MetaRNN

Uncertain

0.63

D;D;D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Uncertain

2.2

.;M;.;.;.

PhyloP100

9.6

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.63

.;N;.;N;N

REVEL

Uncertain

0.34

Sift

Benign

0.046

.;D;.;T;D

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

1.0

.;D;.;.;.

Vest4

0.62

MutPred

0.48

.;Gain of catalytic residue at D459 (P = 0.0031);.;.;.;

MVP

0.77

MPC

0.77

ClinPred

0.56

GERP RS

6.0

Varity_R

0.13

gMVP

0.63

Mutation Taster

=44/56

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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.

13-101714524-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over