NM_001177701.3:c.415C>G

Variant names:

• chr22-36762951-G-C
• rs112218090
• NM_001177701.3:c.415C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001177701.3(IFT27):​c.415C>G​(p.Arg139Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R139Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: IFT27 NM_001177701.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44
• Publications: 3 publications found

Genes affected

IFT27 (HGNC:18626): (intraflagellar transport 27) This gene encodes a GTP-binding protein that is a core component of the intraflagellar transport complex B. Characterization of the similar Chlamydomonas protein indicates a function in cell cycle control. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

CACNG2-DT (HGNC:55682): (CACNG2 divergent transcript)

ACMG classification

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=0.39934385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177701.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT27	NM_001177701.3	MANE Select	c.415C>G	p.Arg139Gly	missense	Exon 6 of 7	NP_001171172.1
	IFT27	NM_001363003.2		c.415C>G	p.Arg139Gly	missense	Exon 7 of 8	NP_001349932.1
	IFT27	NM_006860.5		c.412C>G	p.Arg138Gly	missense	Exon 6 of 7	NP_006851.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT27	ENST00000433985.7	TSL:1 MANE Select	c.415C>G	p.Arg139Gly	missense	Exon 6 of 7	ENSP00000393541.2
	IFT27	ENST00000340630.9	TSL:1	c.412C>G	p.Arg138Gly	missense	Exon 6 of 7	ENSP00000343593.5
	IFT27	ENST00000417951.6	TSL:5	c.532C>G	p.Arg178Gly	missense	Exon 7 of 7	ENSP00000392016.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445910 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717446

African (AFR) AF: 0.00 AC: 0 AN: 33170

American (AMR) AF: 0.00 AC: 0 AN: 43580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39024

South Asian (SAS) AF: 0.00 AC: 0 AN: 83370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102036

Other (OTH) AF: 0.0000167 AC: 1 AN: 59764

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 11

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.4
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.31
Sift	Benign	0.094	T
Sift4G	Benign	0.21	T
Polyphen		0.082	B
Vest4		0.48
MutPred		0.50		Loss of MoRF binding (P = 0.0556)
MVP		0.65
MPC		0.19
ClinPred		0.77	D
GERP RS		5.5
Varity_R		0.39
gMVP		0.32
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs112218090; hg19: chr22-37158995;