chr11-36636083-C-A

Variant names:

• chr11-36636083-C-A
• rs143974880
• NM_138787.4:c.324C>A

Variant summary

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

The NM_138787.4(IFTAP):​c.324C>A​(p.Asp108Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000877 in 1,608,522 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00087 (1 hom.)
• Consequence: IFTAP NM_138787.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.215
• Publications: 8 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011366874).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFTAP	NM_138787.4	MANE Select	c.324C>A	p.Asp108Glu	missense	Exon 4 of 6	NP_620142.2
	IFTAP	NM_001276722.2		c.324C>A	p.Asp108Glu	missense	Exon 4 of 6	NP_001263651.1	Q86VG3-1
	IFTAP	NM_001276723.2		c.324C>A	p.Asp108Glu	missense	Exon 4 of 6	NP_001263652.1	Q86VG3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFTAP	ENST00000334307.10	TSL:1 MANE Select	c.324C>A	p.Asp108Glu	missense	Exon 4 of 6	ENSP00000334848.5	Q86VG3-1
	IFTAP	ENST00000347206.8	TSL:1	c.137-11933C>A		intron	N/A	ENSP00000299442.6	Q86VG3-2
	IFTAP	ENST00000446510.6	TSL:5	c.324C>A	p.Asp108Glu	missense	Exon 4 of 6	ENSP00000403937.3	Q86VG3-1

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000722 AC: 181 AN: 250762 AF XY: 0.000694

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00112

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.000872 AC: 1270 AN: 1456250 Hom.: 1 Cov.: 28 AF XY: 0.000828 AC XY: 600 AN XY: 724852

African (AFR) AF: 0.000210 AC: 7 AN: 33364

American (AMR) AF: 0.00148 AC: 66 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86104

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00104 AC: 1153 AN: 1107088

Other (OTH) AF: 0.000664 AC: 40 AN: 60202

GnomAD4 genome AF: 0.000919 AC: 140 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000913 AC XY: 68 AN XY: 74464

African (AFR) AF: 0.000265 AC: 11 AN: 41556

American (AMR) AF: 0.00347 AC: 53 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00103 AC: 70 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00113

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000618 AC: 75

EpiCase AF: 0.000873

EpiControl AF: 0.00125

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.21
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.083
Sift	Benign	0.21	T
Sift4G	Uncertain	0.014	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.22		Loss of helix (P = 0.1299)
MVP		0.53
MPC		0.20
ClinPred		0.052	T
GERP RS		1.3
Varity_R		0.12
gMVP		0.041
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs143974880; hg19: chr11-36657633; COSMIC: COSV100531141; COSMIC: COSV100531141;