13-73061963-C-G

Variant names:

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

Variant summary

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

The NM_001730.5(KLF5):​c.364C>G​(p.Gln122Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 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. Q122P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KLF5 NM_001730.5 missense
• Clinical Significance: Not reported in ClinVar
• 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>G	p.Gln122Glu	missense	Exon 2 of 4	NP_001721.2
	KLF5	NM_001286818.2		c.91C>G	p.Gln31Glu	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>G	p.Gln122Glu	missense	Exon 2 of 4	ENSP00000366915.4	Q13887-1
	KLF5	ENST00000539231.5	TSL:1	c.91C>G	p.Gln31Glu	missense	Exon 2 of 4	ENSP00000440407.1	Q13887-4
	KLF5	ENST00000851191.1		c.364C>G	p.Gln122Glu	missense	Exon 2 of 3	ENSP00000521250.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461830 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727216

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.039
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.24
Sift	Benign	0.93	T
Sift4G	Benign	1.0	T
Polyphen		0.27	B
Vest4		0.70
MutPred		0.34		Gain of phosphorylation at S118 (P = 0.1713)
MVP		0.67
MPC		0.56
ClinPred		0.69	D
GERP RS		6.0
Varity_R		0.12
gMVP		0.39
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;