15-31327549-G-C

Position:

• chr15-31327549-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015995.4(KLF13):​c.337G>C​(p.Ala113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLF13 NM_015995.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55

Genes affected

KLF13 (HGNC:13672): (KLF transcription factor 13) KLF13 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

KLF13 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08812216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF13	NM_015995.4	c.337G>C	p.Ala113Pro	missense_variant	1/2	ENST00000307145.4	NP_057079.2
KLF13	NM_001302461.2	c.337G>C	p.Ala113Pro	missense_variant	1/2		NP_001289390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF13	ENST00000307145.4	c.337G>C	p.Ala113Pro	missense_variant	1/2	1	NM_015995.4	ENSP00000302456.3
KLF13	ENST00000558921.1	n.-18G>C		upstream_gene_variant		3

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 30, 2021

The c.337G>C (p.A113P) alteration is located in exon 1 (coding exon 1) of the KLF13 gene. This alteration results from a G to C substitution at nucleotide position 337, causing the alanine (A) at amino acid position 113 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	Benign	0.097
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.023
Sift	Benign	0.27	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.065
MutPred		0.33		Gain of glycosylation at A113 (P = 0.0557);
MVP		0.093
MPC		2.5
ClinPred		0.25	T
GERP RS		0.50
Varity_R		0.15
gMVP		0.14

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: chr15-31619752;