13-73061963-C-A

Variant names:

• chr13-73061963-C-A
• rs2139103766
• NM_001730.5:c.364C>A

Variant summary

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

The NM_001730.5(KLF5):​c.364C>A​(p.Gln122Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q122P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLF5 NM_001730.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.87
• Publications: 0 publications found

Genes affected

KLF5 (HGNC:6349): (KLF transcription factor 5) This gene encodes a member of the Kruppel-like factor subfamily of zinc finger proteins. The encoded protein is a transcriptional activator that binds directly to a specific recognition motif in the promoters of target genes. This protein acts downstream of multiple different signaling pathways and is regulated by post-translational modification. It may participate in both promoting and suppressing cell proliferation. Expression of this gene may be changed in a variety of different cancers and in cardiovascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001730.5. 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
	KLF5	NM_001730.5	MANE Select	c.364C>A	p.Gln122Lys	missense	Exon 2 of 4	NP_001721.2
	KLF5	NM_001286818.2		c.91C>A	p.Gln31Lys	missense	Exon 2 of 4	NP_001273747.1	Q13887-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF5	ENST00000377687.6	TSL:1 MANE Select	c.364C>A	p.Gln122Lys	missense	Exon 2 of 4	ENSP00000366915.4	Q13887-1
	KLF5	ENST00000539231.5	TSL:1	c.91C>A	p.Gln31Lys	missense	Exon 2 of 4	ENSP00000440407.1	Q13887-4
	KLF5	ENST00000851191.1		c.364C>A	p.Gln122Lys	missense	Exon 2 of 3	ENSP00000521250.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.24
Sift	Benign	0.042	D
Sift4G	Benign	0.13	T
Polyphen		0.96	D
Vest4		0.68
MutPred		0.48		Gain of methylation at Q122 (P = 0.0016)
MVP		0.62
MPC		0.69
ClinPred		0.82	D
GERP RS		6.0
Varity_R		0.29
gMVP		0.51
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: rs2139103766; hg19: chr13-73636101;