Variant chr19-1863268-T-G 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.230A>C(p.His77Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000147 in 135,664 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 (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 30)

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: -1.81

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:

Genome browser will be placed here

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=0.07638565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF16	NM_031918.4 linkuse as main transcript	c.230A>C	p.His77Pro	missense_variant	1/2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 linkuse as main transcript	c.428-8508A>C		intron_variant			XP_047295454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLF16	ENST00000250916.6 linkuse as main transcript	c.230A>C	p.His77Pro	missense_variant	1/2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 linkuse as main transcript	c.230A>C	p.His77Pro	missense_variant	1/3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 linkuse as main transcript	n.230A>C		non_coding_transcript_exon_variant	1/3	1		ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes

AF:

0.0000148

AC:

AN:

135534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000249

Gnomad SAS

AF:

0.000257

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

852228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

395462

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

AF:

0.0000147

AC:

AN:

135664

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

65842

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000249

Gnomad4 SAS

AF:

0.000256

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 16, 2021

The c.230A>C (p.H77P) alteration is located in exon 1 (coding exon 1) of the KLF16 gene. This alteration results from a A to C substitution at nucleotide position 230, causing the histidine (H) at amino acid position 77 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

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.020

Sift

Benign

0.35

T;.

Sift4G

Benign

0.22

T;T

Polyphen

0.0

B;B

Vest4

0.099

MutPred

0.42

Gain of glycosylation at H77 (P = 0.0068);Gain of glycosylation at H77 (P = 0.0068);

MVP

0.17

MPC

2.2

ClinPred

0.087

GERP RS

0.68

Varity_R

0.20

gMVP

0.28

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