13-73061964-A-C

Position:

• chr13-73061964-A-C

Variant summary

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

The NM_001730.5(KLF5):​c.365A>C​(p.Gln122Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar 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: 7.00

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]

KLF5 (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
KLF5	NM_001730.5	c.365A>C	p.Gln122Pro	missense_variant	2/4	ENST00000377687.6	NP_001721.2
KLF5	NM_001286818.2	c.92A>C	p.Gln31Pro	missense_variant	2/4		NP_001273747.1
KLF5	XM_047430553.1	c.143A>C	p.Gln48Pro	missense_variant	2/4		XP_047286509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF5	ENST00000377687.6	c.365A>C	p.Gln122Pro	missense_variant	2/4	1	NM_001730.5	ENSP00000366915.4
KLF5	ENST00000539231.5	c.92A>C	p.Gln31Pro	missense_variant	2/4	1		ENSP00000440407.1
KLF5	ENST00000476859.1	n.189A>C		non_coding_transcript_exon_variant	2/2	3
KLF5	ENST00000477333.5	n.287A>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.365A>C (p.Q122P) alteration is located in exon 2 (coding exon 2) of the KLF5 gene. This alteration results from a A to C substitution at nucleotide position 365, causing the glutamine (Q) at amino acid position 122 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.28	.;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	.;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.29
Sift	Benign	0.20	T;T
Sift4G	Benign	0.23	T;T
Polyphen		1.0	.;D
Vest4		0.79
MutPred		0.41		.;Loss of stability (P = 0.1544);
MVP		0.80
MPC		0.80
ClinPred		0.85	D
GERP RS		6.0
Varity_R		0.37
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-73636102;