15-31327584-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015995.4(KLF13):c.372G>C(p.Glu124Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00442 in 1,219,838 control chromosomes in the GnomAD database, including 17 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 17 hom. )

Consequence

KLF13
NM_015995.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.33

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009457856).

BP6

Variant 15-31327584-G-C is Benign according to our data. Variant chr15-31327584-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 726688.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS2

High AC in GnomAd at 365 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF13	NM_015995.4 linkuse as main transcript	c.372G>C	p.Glu124Asp	missense_variant	1/2	ENST00000307145.4
KLF13	NM_001302461.2 linkuse as main transcript	c.372G>C	p.Glu124Asp	missense_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF13	ENST00000307145.4 linkuse as main transcript	c.372G>C	p.Glu124Asp	missense_variant	1/2	1	NM_015995.4	P1
KLF13	ENST00000558921.1 linkuse as main transcript	n.18G>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00246

AC:

365

AN:

148602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000951

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000600

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000981

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00455

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00174

AC:

AN:

8032

Hom.:

AF XY:

0.00173

AC XY:

AN XY:

4054

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:

0.00

Gnomad FIN exome

AF:

0.00206

Gnomad NFE exome

AF:

0.00206

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00469

AC:

5026

AN:

1071130

Hom.:

Cov.:

AF XY:

0.00451

AC XY:

2313

AN XY:

513142

show subpopulations

Gnomad4 AFR exome

AF:

0.000910

Gnomad4 AMR exome

AF:

0.000567

Gnomad4 ASJ exome

AF:

0.00351

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000181

Gnomad4 FIN exome

AF:

0.00184

Gnomad4 NFE exome

AF:

0.00529

Gnomad4 OTH exome

AF:

0.00297

GnomAD4 genome

AF:

0.00245

AC:

365

AN:

148708

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

156

AN XY:

72582

show subpopulations

Gnomad4 AFR

AF:

0.000949

Gnomad4 AMR

AF:

0.000599

Gnomad4 ASJ

AF:

0.00116

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000981

Gnomad4 NFE

AF:

0.00455

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00159

Hom.:

Bravo

AF:

0.00234

ExAC

AF:

0.000623

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.372G>C (p.E124D) 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 372, causing the glutamic acid (E) at amino acid position 124 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Benign

0.90

DEOGEN2

Benign

0.071

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.28

M_CAP

Benign

0.012

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.070

REVEL

Benign

0.028

Sift

Benign

0.43

Sift4G

Benign

0.62

Polyphen

0.17

Vest4

0.10

MutPred

0.36

Loss of glycosylation at P125 (P = 0.08);

MVP

0.31

MPC

1.4

ClinPred

0.030

GERP RS

0.45

Varity_R

0.050

gMVP

0.12

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

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