Variant 19-1854725-C-G 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.493G>C(p.Asp165His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

KLF16
NM_031918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

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.493G>C	p.Asp165His	missense_variant	2/2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 linkuse as main transcript	c.463G>C	p.Asp155His	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.493G>C	p.Asp165His	missense_variant	2/2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 linkuse as main transcript	c.493G>C	p.Asp165His	missense_variant	2/3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 linkuse as main transcript	n.493G>C		non_coding_transcript_exon_variant	2/3	1		ENSP00000439973.1	Q9BXK1
KLF16	ENST00000592313.1 linkuse as main transcript	c.82G>C	p.Asp28His	missense_variant	2/2	3		ENSP00000480570.1	A0A087WWX5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1446052

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719850

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

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

Apr 20, 2023

The c.493G>C (p.D165H) alteration is located in exon 2 (coding exon 2) of the KLF16 gene. This alteration results from a G to C substitution at nucleotide position 493, causing the aspartic acid (D) at amino acid position 165 to be replaced by a histidine (H). 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

0.63

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.085

T;T;.

Eigen

Benign

0.031

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.82

.;T;T

M_CAP

Pathogenic

0.68

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

1.7

L;L;.

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.6

D;.;.

REVEL

Uncertain

0.43

Sift

Benign

0.12

T;.;.

Sift4G

Uncertain

0.028

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.14

MutPred

0.64

Gain of MoRF binding (P = 0.0411);Gain of MoRF binding (P = 0.0411);.;

MVP

0.99

MPC

2.7

ClinPred

0.99

GERP RS

2.2

Varity_R

0.15

gMVP

0.50

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