15-31327544-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015995.4(KLF13):c.332A>C(p.Glu111Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000105 in 956,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. E111D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: KLF13 NM_015995.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.267

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0573999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF13	NM_015995.4	c.332A>C	p.Glu111Ala	missense_variant	1/2	ENST00000307145.4
KLF13	NM_001302461.2	c.332A>C	p.Glu111Ala	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF13	ENST00000307145.4	c.332A>C	p.Glu111Ala	missense_variant	1/2	1	NM_015995.4	P1
KLF13	ENST00000558921.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000105 AC: 1 AN: 956748 Hom.: 0 Cov.: 32 AF XY: 0.00000222 AC XY: 1 AN XY: 449546

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

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 13, 2021

The c.332A>C (p.E111A) alteration is located in exon 1 (coding exon 1) of the KLF13 gene. This alteration results from a A to C substitution at nucleotide position 332, causing the glutamic acid (E) at amino acid position 111 to be replaced by an alanine (A). 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	0.072
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	11
Dann	Benign	0.80
DEOGEN2	Benign	0.064	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.90	N
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.010	N
REVEL	Benign	0.026
Sift	Benign	0.25	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.040
MutPred		0.41		Gain of glycosylation at P108 (P = 0.1325);
MVP		0.10
MPC		1.7
ClinPred		0.059	T
GERP RS		-3.7
Varity_R		0.041
gMVP		0.16

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: chr15-31619747;