Variant 15-31327328-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015995.4(KLF13):c.116C>T(p.Ala39Val) variant causes a missense change. The variant allele was found at a frequency of 0.000549 in 1,279,802 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 1 hom. )

Consequence

KLF13
NM_015995.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021924734).

BS2

High AC in GnomAd4 at 53 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF13	NM_015995.4 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/2	ENST00000307145.4	NP_057079.2	Q9Y2Y9X5DNR2
KLF13	NM_001302461.2 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/2		NP_001289390.1	Q9Y2Y9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF13	ENST00000307145.4 linkuse as main transcript	c.116C>T	p.Ala39Val	missense_variant	1/2	1	NM_015995.4	ENSP00000302456.3		Q9Y2Y9

Frequencies

GnomAD3 genomes

AF:

0.000353

AC:

AN:

150116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000580

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000551

AC:

AN:

5442

Hom.:

AF XY:

0.000797

AC XY:

AN XY:

3762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00129

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000390

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000575

AC:

650

AN:

1129578

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

331

AN XY:

547408

show subpopulations

Gnomad4 AFR exome

AF:

0.000134

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00191

Gnomad4 FIN exome

AF:

0.000165

Gnomad4 NFE exome

AF:

0.000577

Gnomad4 OTH exome

AF:

0.000517

GnomAD4 genome

AF:

0.000353

AC:

AN:

150224

Hom.:

Cov.:

AF XY:

0.000354

AC XY:

AN XY:

73384

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000660

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000204

Gnomad4 NFE

AF:

0.000580

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.000246

ExAC

AF:

0.000571

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.116C>T (p.A39V) alteration is located in exon 1 (coding exon 1) of the KLF13 gene. This alteration results from a C to T substitution at nucleotide position 116, causing the alanine (A) at amino acid position 39 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.32

M_CAP

Benign

0.0086

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.33

REVEL

Benign

0.083

Sift

Benign

0.17

Sift4G

Benign

0.36

Polyphen

0.38

Vest4

0.14

MutPred

0.22

Loss of helix (P = 0.1706);

MVP

0.16

MPC

1.5

ClinPred

0.090

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.054

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over