20-43635933-G-C

Variant names:

• chr20-43635933-G-C
• rs145672738
• NM_016004.5:c.931G>C
• IFT52 p.Glu311Gln

Variant summary

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

The NM_016004.5(IFT52):​c.931G>C​(p.Glu311Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. E311G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: IFT52 NM_016004.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.60
• Publications: 3 publications found

Genes affected

IFT52 (HGNC:15901): (intraflagellar transport 52) This gene encodes a conserved proline-rich protein that is a component of the intraflagellar transport-B (IFT-B) core complex. The encoded protein is essential for the integrity of the IFT-B core complex, and for biosynthesis and maintenance of cilia. Mutations in this gene are associated with ciliopathy that affects the skeleton. [provided by RefSeq, Oct 2016]

IFT52 Gene-Disease associations (from GenCC):

• short-rib thoracic dysplasia 16 with or without polydactyly

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• cranioectodermal dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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=0.38669816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016004.5. 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
	IFT52	NM_016004.5	MANE Select	c.931G>C	p.Glu311Gln	missense	Exon 11 of 14	NP_057088.2	Q9Y366
	IFT52	NM_001303458.3		c.931G>C	p.Glu311Gln	missense	Exon 11 of 14	NP_001290387.1	Q9Y366
	IFT52	NM_001303459.3		c.931G>C	p.Glu311Gln	missense	Exon 11 of 13	NP_001290388.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT52	ENST00000373030.8	TSL:1 MANE Select	c.931G>C	p.Glu311Gln	missense	Exon 11 of 14	ENSP00000362121.3	Q9Y366
	IFT52	ENST00000871354.1		c.1030G>C	p.Glu344Gln	missense	Exon 12 of 15	ENSP00000541413.1
	IFT52	ENST00000871357.1		c.1030G>C	p.Glu344Gln	missense	Exon 12 of 15	ENSP00000541416.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	0.0027	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.075
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.32
Mutation Taster		=82/18	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs145672738;

hg19: chr20-42264573;