Variant 19-1854596-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031918.4(KLF16):c.622C>T(p.Arg208Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,698 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KLF16
NM_031918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF16	NM_031918.4 linkuse as main transcript	c.622C>T	p.Arg208Cys	missense_variant	2/2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 linkuse as main transcript	c.592C>T	p.Arg198Cys	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.622C>T	p.Arg208Cys	missense_variant	2/2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 linkuse as main transcript	c.622C>T	p.Arg208Cys	missense_variant	2/3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 linkuse as main transcript	n.622C>T		non_coding_transcript_exon_variant	2/3	1		ENSP00000439973.1	Q9BXK1
KLF16	ENST00000592313.1 linkuse as main transcript	c.211C>T	p.Arg71Cys	missense_variant	2/2	3		ENSP00000480570.1	A0A087WWX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.94e-7

AC:

AN:

1440698

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

716848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

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.:

Bravo

AF:

0.00000378

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

Sep 27, 2024

The c.622C>T (p.R208C) alteration is located in exon 2 (coding exon 2) of the KLF16 gene. This alteration results from a C to T substitution at nucleotide position 622, causing the arginine (R) at amino acid position 208 to be replaced by a cysteine (C). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.031

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.069

T;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.45

LIST_S2

Pathogenic

0.98

.;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.3

M;M;.

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-7.2

D;.;.

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.36

MutPred

0.47

Loss of MoRF binding (P = 0.0078);Loss of MoRF binding (P = 0.0078);.;

MVP

0.58

MPC

1.7

ClinPred

0.97

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.2

Varity_R

0.57

gMVP

0.75

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