Genetic Variant NM_138787.4:c.143A>G (chr11-36633290-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_138787.4(IFTAP):c.143A>G(p.His48Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000778 in 1,543,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

IFTAP
NM_138787.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.205

Publications

0 publications found

Variant links:

Genes affected

IFTAP (HGNC:25142): (intraflagellar transport associated protein) This gene encodes a protein that was identified as a cellular interacting partner of non-structural protein 10 of the severe acute respiratory syndrome coronavirus (SARS-CoV). The encoded protein may function as a negative regulator of transcription. There is a pseudogene for this gene on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

IFTAP 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=0.02184537).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138787.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFTAP	NM_138787.4	MANE Select	c.143A>G	p.His48Arg	missense	Exon 3 of 6	NP_620142.2
IFTAP	NM_001276722.2		c.143A>G	p.His48Arg	missense	Exon 3 of 6	NP_001263651.1	Q86VG3-1
IFTAP	NM_001276723.2		c.143A>G	p.His48Arg	missense	Exon 3 of 6	NP_001263652.1	Q86VG3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFTAP	ENST00000334307.10	TSL:1 MANE Select	c.143A>G	p.His48Arg	missense	Exon 3 of 6	ENSP00000334848.5	Q86VG3-1
IFTAP	ENST00000347206.8	TSL:1	c.137-14726A>G		intron	N/A	ENSP00000299442.6	Q86VG3-2
IFTAP	ENST00000446510.6	TSL:5	c.143A>G	p.His48Arg	missense	Exon 3 of 6	ENSP00000403937.3	Q86VG3-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000130

AC:

AN:

207124

AF XY:

0.000169

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000128

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.000214

GnomAD4 exome

AF:

0.0000791

AC:

110

AN:

1390784

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

689406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30152

American (AMR)

AF:

0.0000587

AC:

AN:

34058

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24042

East Asian (EAS)

AF:

0.00

AC:

AN:

36898

South Asian (SAS)

AF:

0.0000141

AC:

AN:

70710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51824

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

4530

European-Non Finnish (NFE)

AF:

0.0000832

AC:

AN:

1081280

Other (OTH)

AF:

0.000105

AC:

AN:

57290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.000327

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67954

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.0000961

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.0

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.0083

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.40

M_CAP

Benign

0.0033

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

0.20

PROVEAN

Benign

-0.33

REVEL

Benign

0.029

Sift

Benign

0.79

Sift4G

Benign

0.16

Polyphen

0.0040

Vest4

0.076

MVP

0.055

MPC

0.029

ClinPred

0.016

GERP RS

1.1

Varity_R

0.031

gMVP

0.032

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over