Variant 19-1854473-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031918.4(KLF16):c.745C>A(p.Pro249Thr) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLF16
NM_031918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

KLF16 (HGNC:16857): (KLF transcription factor 16) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within dopamine receptor signaling pathway. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

KLF16 links:

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ACMG classification

Classification made for transcript

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=0.13064805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF16	NM_031918.4 linkuse as main transcript	c.745C>A	p.Pro249Thr	missense_variant	2/2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 linkuse as main transcript	c.715C>A	p.Pro239Thr	missense_variant	2/2		XP_047295454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLF16	ENST00000250916.6 linkuse as main transcript	c.745C>A	p.Pro249Thr	missense_variant	2/2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 linkuse as main transcript	c.745C>A	p.Pro249Thr	missense_variant	2/3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 linkuse as main transcript	n.745C>A		non_coding_transcript_exon_variant	2/3	1		ENSP00000439973.1	Q9BXK1
KLF16	ENST00000592313.1 linkuse as main transcript	c.334C>A	p.Pro112Thr	missense_variant	2/2	3		ENSP00000480570.1	A0A087WWX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1266928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

617352

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 19, 2024

The c.745C>A (p.P249T) alteration is located in exon 2 (coding exon 2) of the KLF16 gene. This alteration results from a C to A substitution at nucleotide position 745, causing the proline (P) at amino acid position 249 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

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0085

T;T;.

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.52

.;T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.0

N;.;.

REVEL

Benign

0.058

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.064

B;B;.

Vest4

0.16

MutPred

0.31

Gain of phosphorylation at P249 (P = 0.0115);Gain of phosphorylation at P249 (P = 0.0115);.;

MVP

0.24

MPC

1.4

ClinPred

0.24

GERP RS

2.4

Varity_R

0.24

gMVP

0.42

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over