chr22-36758315-G-A

Variant names:

• chr22-36758315-G-A
• rs1211294837
• NM_001177701.3:c.557C>T

Variant summary

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

The NM_001177701.3(IFT27):​c.557C>T​(p.Ala186Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. A186E) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: IFT27 NM_001177701.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 0 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: 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=0.046599597).

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.557C>T	p.Ala186Val	missense	Exon 7 of 7	NP_001171172.1	Q9BW83-1
	IFT27	NM_001363003.2		c.557C>T	p.Ala186Val	missense	Exon 8 of 8	NP_001349932.1	Q9BW83-1
	IFT27	NM_006860.5		c.554C>T	p.Ala185Val	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.557C>T	p.Ala186Val	missense	Exon 7 of 7	ENSP00000393541.2	Q9BW83-1
	IFT27	ENST00000340630.9	TSL:1	c.554C>T	p.Ala185Val	missense	Exon 7 of 7	ENSP00000343593.5	Q9BW83-2
	IFT27	ENST00000916904.1		c.671C>T	p.Ala224Val	missense	Exon 8 of 8	ENSP00000586963.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41466

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.3
DANN	Benign	0.96
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PhyloP100		1.1
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.066
Sift	Benign	0.21	T
Sift4G	Uncertain	0.015	D
Polyphen		0.0	B
Vest4		0.089
MutPred		0.39		Loss of disorder (P = 0.0963)
MVP		0.088
MPC		0.092
ClinPred		0.11	T
GERP RS		0.73
Varity_R		0.022
gMVP		0.20
Mutation Taster		=95/5	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: rs1211294837; hg19: chr22-37154359;