rs140440023

Variant names:

• chr22-36758324-C-G
• rs140440023
• NM_001177701.3:c.548G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-36758324-C-G
• chr22-36758324-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001177701.3(IFT27):​c.548G>C​(p.Arg183Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R183W) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IFT27 NM_001177701.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09235981).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT27	NM_001177701.3	MANE Select	c.548G>C	p.Arg183Pro	missense	Exon 7 of 7	NP_001171172.1	Q9BW83-1
	IFT27	NM_001363003.2		c.548G>C	p.Arg183Pro	missense	Exon 8 of 8	NP_001349932.1	Q9BW83-1
	IFT27	NM_006860.5		c.545G>C	p.Arg182Pro	missense	Exon 7 of 7	NP_006851.1	Q9BW83-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT27	ENST00000433985.7	TSL:1 MANE Select	c.548G>C	p.Arg183Pro	missense	Exon 7 of 7	ENSP00000393541.2	Q9BW83-1
	IFT27	ENST00000340630.9	TSL:1	c.545G>C	p.Arg182Pro	missense	Exon 7 of 7	ENSP00000343593.5	Q9BW83-2
	IFT27	ENST00000916904.1		c.662G>C	p.Arg221Pro	missense	Exon 8 of 8	ENSP00000586963.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251494 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461738 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111886

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.62
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.061
Sift	Benign	0.095	T
Sift4G	Benign	0.093	T
Polyphen		0.15	B
Vest4		0.25
MutPred		0.45		Loss of MoRF binding (P = 2e-04)
MVP		0.18
MPC		0.21
ClinPred		0.10	T
GERP RS		3.1
Varity_R		0.26
gMVP		0.48
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs140440023; hg19: chr22-37154368;