Genetic Variant KLF16:p.Ala107Ser (chr19-1863179-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031918.4(KLF16):c.319G>T(p.Ala107Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,217,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

KLF16
NM_031918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.286

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017029583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031918.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF16	NM_031918.4	MANE Select	c.319G>T	p.Ala107Ser	missense	Exon 1 of 2	NP_114124.1	Q9BXK1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLF16	ENST00000250916.6	TSL:1 MANE Select	c.319G>T	p.Ala107Ser	missense	Exon 1 of 2	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1	TSL:1	c.319G>T	p.Ala107Ser	missense	Exon 1 of 3	ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5	TSL:1	n.319G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146084

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:

0.00

Gnomad SAS

AF:

0.000420

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000975

AC:

AN:

30756

AF XY:

0.000118

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000747

AC:

AN:

1071602

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

517860

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20722

American (AMR)

AF:

0.00

AC:

AN:

9224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12778

East Asian (EAS)

AF:

0.00

AC:

AN:

20730

South Asian (SAS)

AF:

0.000219

AC:

AN:

31896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2694

European-Non Finnish (NFE)

AF:

0.00000111

AC:

AN:

901088

Other (OTH)

AF:

0.00

AC:

AN:

39906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.581

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146180

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40420

American (AMR)

AF:

0.00

AC:

AN:

14814

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3414

East Asian (EAS)

AF:

0.00

AC:

AN:

4976

South Asian (SAS)

AF:

0.000421

AC:

AN:

4756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65946

Other (OTH)

AF:

0.00

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000397

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.33

M_CAP

Benign

0.012

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.5

PhyloP100

0.29

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.18

REVEL

Benign

0.0080

Sift

Benign

0.95

Sift4G

Benign

0.56

Polyphen

0.026

Vest4

0.18

MutPred

0.35

Gain of phosphorylation at A107 (P = 4e-04)

MVP

0.16

MPC

1.2

ClinPred

0.028

GERP RS

-0.25

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.036

gMVP

0.26

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over