Genetic Variant IFT81:p.Ser2Gly (chr12-110127384-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_014055.4(IFT81):c.4A>G(p.Ser2Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S2S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IFT81
NM_014055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

Publications

0 publications found

Variant links:

Genes affected

IFT81 (HGNC:14313): (intraflagellar transport 81) The protein encoded by this gene, together with IFT74, forms a tubulin-binding module of intraflagellar transport complex B. This module is involved in transport of tubulin within the cilium, and the encoded protein is required for ciliogenesis. Mutations in this gene are a cause of short-rib polydactyly syndromes. [provided by RefSeq, Dec 2016]

IFT81 Gene-Disease associations (from GenCC):

short-rib thoracic dysplasia 19 with or without polydactyly
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: Franklin by Genoox

IFT81 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27109313).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014055.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFT81	NM_014055.4	MANE Select	c.4A>G	p.Ser2Gly	missense	Exon 2 of 19	NP_054774.2
IFT81	NM_001143779.2		c.4A>G	p.Ser2Gly	missense	Exon 2 of 19	NP_001137251.1	Q8WYA0-1
IFT81	NM_001347946.2		c.4A>G	p.Ser2Gly	missense	Exon 2 of 12	NP_001334875.1	Q8WYA0-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFT81	ENST00000242591.10	TSL:1 MANE Select	c.4A>G	p.Ser2Gly	missense	Exon 2 of 19	ENSP00000242591.5	Q8WYA0-1
IFT81	ENST00000552912.5	TSL:1	c.4A>G	p.Ser2Gly	missense	Exon 2 of 19	ENSP00000449718.1	Q8WYA0-1
IFT81	ENST00000361948.8	TSL:1	c.4A>G	p.Ser2Gly	missense	Exon 2 of 12	ENSP00000355372.4	Q8WYA0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1421224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705608

African (AFR)

AF:

0.00

AC:

AN:

31444

American (AMR)

AF:

0.00

AC:

AN:

35208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24506

East Asian (EAS)

AF:

0.00

AC:

AN:

38664

South Asian (SAS)

AF:

0.00

AC:

AN:

78854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096350

Other (OTH)

AF:

0.00

AC:

AN:

58542

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

M_CAP

Benign

0.0079

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

5.0

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.047

Sift

Benign

0.070

Sift4G

Benign

0.31

Polyphen

0.0030

Vest4

0.23

MutPred

0.30

Gain of catalytic residue at I5 (P = 0)

MVP

0.47

MPC

0.56

ClinPred

0.91

GERP RS

6.2

Varity_R

0.22

gMVP

0.42

Mutation Taster

=20/80

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over