11-6608939-C-A

Position:

• chr11-6608939-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004517.4(ILK):​c.504C>A​(p.Phe168Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ILK NM_004517.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14

Genes affected

ILK (HGNC:6040): (integrin linked kinase) This gene encodes a protein with a kinase-like domain and four ankyrin-like repeats. The encoded protein associates at the cell membrane with the cytoplasmic domain of beta integrins, where it regulates integrin-mediated signal transduction. Activity of this protein is important in the epithelial to mesenchymal transition, and over-expression of this gene is implicated in tumor growth and metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

TAF10 (HGNC:11543): (TATA-box binding protein associated factor 10) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the small subunits of TFIID that is associated with a subset of TFIID complexes. Studies with human and mammalian cells have shown that this subunit is required for transcriptional activation by the estrogen receptor, for progression through the cell cycle, and may also be required for certain cellular differentiation programs. [provided by RefSeq, Jul 2008]

ENSG00000254641 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ILK	NM_004517.4	c.504C>A	p.Phe168Leu	missense_variant	6/13	ENST00000299421.9	NP_004508.1
TAF10	NM_006284.4	c.*1983G>T		3_prime_UTR_variant	5/5	ENST00000299424.9	NP_006275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ILK	ENST00000299421.9	c.504C>A	p.Phe168Leu	missense_variant	6/13	1	NM_004517.4	ENSP00000299421.4
TAF10	ENST00000299424	c.*1983G>T		3_prime_UTR_variant	5/5	1	NM_006284.4	ENSP00000299424.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.14	.;T;T;T;T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D;.;D;.;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.55	T
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.42	.;N;.;N;N
REVEL	Uncertain	0.42
Sift	Benign	0.78	.;T;.;T;T
Sift4G	Benign	0.26	T;T;T;T;T
Polyphen		0.11	.;B;.;B;B
Vest4		0.80
MutPred		0.57		.;Loss of methylation at K170 (P = 0.0725);.;Loss of methylation at K170 (P = 0.0725);Loss of methylation at K170 (P = 0.0725);
MVP		0.82
MPC		0.36
ClinPred		0.93	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.49
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554898796; hg19: chr11-6630170;