7-139161018-A-G

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_ModeratePP5_Moderate

The NM_024926.4(IFT56):c.788A>G(p.Asn263Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

IFT56
NM_024926.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 8.05

Publications

0 publications found

Variant links:

Genes affected

IFT56 (HGNC:21882): (intraflagellar transport 56) Predicted to enable intraciliary transport particle B binding activity. Predicted to be involved in cilium organization; protein localization to cilium; and smoothened signaling pathway. Predicted to act upstream of or within manchette assembly. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle B. Predicted to be active in ciliary basal body and ciliary base. [provided by Alliance of Genome Resources, Apr 2022]

IFT56 Gene-Disease associations (from GenCC):

biliary, renal, neurologic, and skeletal syndrome
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

IFT56 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.857

PP5

Variant 7-139161018-A-G is Pathogenic according to our data. Variant chr7-139161018-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 917964.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT56	NM_024926.4 link	c.788A>G	p.Asn263Ser	missense_variant	Exon 8 of 18	ENST00000464848.5	NP_079202.2	A0AVF1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT56	ENST00000464848.5 link	c.788A>G	p.Asn263Ser	missense_variant	Exon 8 of 18	1	NM_024926.4	ENSP00000419279.1		A0AVF1-1
IFT56	ENST00000478836.6 link	c.470A>G	p.Asn157Ser	missense_variant	Exon 6 of 16	2		ENSP00000419178.2		B7Z6R6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461324

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726974

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53314

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111716

Other (OTH)

AF:

0.0000166

AC:

AN:

60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Biliary, renal, neurologic, and skeletal syndrome

Pathogenic:2

Oct 04, 2021

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Mar 17, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:research

- -

Caroli disease

Pathogenic:1

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.0027

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;T;T;T;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Pathogenic

0.86

D;D;D;D;D

MetaSVM

Uncertain

0.45

PhyloP100

8.1

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.9

D;D;D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0, 0.98, 0.99

.;D;D;D;.

Vest4

0.81

MutPred

0.60

Gain of phosphorylation at N263 (P = 0.0499);Gain of phosphorylation at N263 (P = 0.0499);.;Gain of phosphorylation at N263 (P = 0.0499);.;

MVP

0.86

MPC

0.61

ClinPred

1.0

GERP RS

4.9

Varity_R

0.69

gMVP

0.75

Mutation Taster

=1/99

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.20

Position offset: 4

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

Publications

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7-139161018-A-G

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