11-36636083-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_138787.4(IFTAP):​c.324C>T​(p.Asp108Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IFTAP NM_138787.4 synonymous
• Clinical Significance: Not reported in ClinVar
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=0.215 with no splicing effect.

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>T	p.Asp108Asp	synonymous	Exon 4 of 6	NP_620142.2
	IFTAP	NM_001276722.2		c.324C>T	p.Asp108Asp	synonymous	Exon 4 of 6	NP_001263651.1	Q86VG3-1
	IFTAP	NM_001276723.2		c.324C>T	p.Asp108Asp	synonymous	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>T	p.Asp108Asp	synonymous	Exon 4 of 6	ENSP00000334848.5	Q86VG3-1
	IFTAP	ENST00000347206.8	TSL:1	c.137-11933C>T		intron	N/A	ENSP00000299442.6	Q86VG3-2
	IFTAP	ENST00000446510.6	TSL:5	c.324C>T	p.Asp108Asp	synonymous	Exon 4 of 6	ENSP00000403937.3	Q86VG3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250762 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456360 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724904

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

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 53364

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

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107198

Other (OTH) AF: 0.00 AC: 0 AN: 60202

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.92
DANN	Benign	0.38
PhyloP100		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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;