NM_015662.3:c.5059C>T

Variant names:

• chr2-27445305-G-A
• rs917873749
• NM_015662.3:c.5059C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_015662.3(IFT172):​c.5059C>T​(p.Leu1687Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,611,916 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: IFT172 NM_015662.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

Genes affected

IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]

KRTCAP3 (HGNC:28943): (keratinocyte associated protein 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.32695207).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015662.3. 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
	IFT172	NM_015662.3	MANE Select	c.5059C>T	p.Leu1687Phe	missense	Exon 46 of 48	NP_056477.1	Q9UG01-1
	IFT172	NM_001410739.1		c.4993C>T	p.Leu1665Phe	missense	Exon 46 of 48	NP_001397668.1	A0A6Q8PGJ2
	KRTCAP3	NM_001168364.2		c.*6-996G>A		intron	N/A	NP_001161836.1	Q53RY4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT172	ENST00000260570.8	TSL:1 MANE Select	c.5059C>T	p.Leu1687Phe	missense	Exon 46 of 48	ENSP00000260570.3	Q9UG01-1
	IFT172	ENST00000509128.5	TSL:1	n.*504C>T		non_coding_transcript_exon	Exon 14 of 16	ENSP00000427255.1	H0YAI8
	IFT172	ENST00000509128.5	TSL:1	n.*504C>T		3_prime_UTR	Exon 14 of 16	ENSP00000427255.1	H0YAI8

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152136 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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1459780 Hom.: 0 Cov.: 32 AF XY: 0.00000551 AC XY: 4 AN XY: 725916

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.000182 AC: 1 AN: 5508

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110818

Other (OTH) AF: 0.0000166 AC: 1 AN: 60228

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68030

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

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	IFT172-related disorder (1)
-	1	-	Inborn genetic diseases (1)
-	1	-	Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71 (1)
-	1	-	Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71;C4310707:Bardet-Biedl syndrome 20 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.053
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.81	P
Vest4		0.51
MVP		0.46
MPC		0.58
ClinPred		0.82	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.50
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs917873749; hg19: chr2-27668172;