11-36633290-A-C

Variant names:

• chr11-36633290-A-C
• rs149036446
• NM_138787.4:c.143A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138787.4(IFTAP):​c.143A>C​(p.His48Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H48R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFTAP NM_138787.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 0 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045591623).

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.143A>C	p.His48Pro	missense	Exon 3 of 6	NP_620142.2
	IFTAP	NM_001276722.2		c.143A>C	p.His48Pro	missense	Exon 3 of 6	NP_001263651.1	Q86VG3-1
	IFTAP	NM_001276723.2		c.143A>C	p.His48Pro	missense	Exon 3 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.143A>C	p.His48Pro	missense	Exon 3 of 6	ENSP00000334848.5	Q86VG3-1
	IFTAP	ENST00000347206.8	TSL:1	c.137-14726A>C		intron	N/A	ENSP00000299442.6	Q86VG3-2
	IFTAP	ENST00000446510.6	TSL:5	c.143A>C	p.His48Pro	missense	Exon 3 of 6	ENSP00000403937.3	Q86VG3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000192 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.1
DANN	Benign	0.14
DEOGEN2	Benign	0.091	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.20
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.079
Sift	Benign	0.31	T
Sift4G	Benign	0.095	T
Polyphen		0.015	B
Vest4		0.13
MutPred		0.19		Gain of glycosylation at S50 (P = 0.0851)
MVP		0.055
MPC		0.034
ClinPred		0.057	T
GERP RS		1.1
Varity_R		0.27
gMVP		0.16
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs149036446; hg19: chr11-36654840;