13-73062213-A-C

Position:

• chr13-73062213-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001730.5(KLF5):​c.614A>C​(p.Asn205Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 3.82

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33381662).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF5	NM_001730.5	c.614A>C	p.Asn205Thr	missense_variant	2/4	ENST00000377687.6	NP_001721.2
KLF5	NM_001286818.2	c.341A>C	p.Asn114Thr	missense_variant	2/4		NP_001273747.1
KLF5	XM_047430553.1	c.392A>C	p.Asn131Thr	missense_variant	2/4		XP_047286509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF5	ENST00000377687.6	c.614A>C	p.Asn205Thr	missense_variant	2/4	1	NM_001730.5	ENSP00000366915.4
KLF5	ENST00000539231.5	c.341A>C	p.Asn114Thr	missense_variant	2/4	1		ENSP00000440407.1
KLF5	ENST00000476859.1	n.438A>C		non_coding_transcript_exon_variant	2/2	3
KLF5	ENST00000477333.5	n.536A>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

Sep 27, 2022

The c.614A>C (p.N205T) 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 614, causing the asparagine (N) at amino acid position 205 to be replaced by a threonine (T). 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	Uncertain	0.45
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D;D
Sift4G	Uncertain	0.017	D;D
Polyphen		0.98	.;D
Vest4		0.47
MutPred		0.42		.;Gain of glycosylation at N205 (P = 0.0289);
MVP		0.30
MPC		0.81
ClinPred		0.93	D
GERP RS		5.7
Varity_R		0.31
gMVP		0.28

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: chr13-73636351;