Variant 19-1863188-A-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.310T>C(p.Ser104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000968 in 1,033,186 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: not found (cov: 30)

Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

KLF16
NM_031918.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.164

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=0.11478078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF16	NM_031918.4 linkuse as main transcript	c.310T>C	p.Ser104Pro	missense_variant	1/2	ENST00000250916.6	NP_114124.1	Q9BXK1
KLF16	XM_047439498.1 linkuse as main transcript	c.428-8428T>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.310T>C	p.Ser104Pro	missense_variant	1/2	1	NM_031918.4	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1 linkuse as main transcript	c.310T>C	p.Ser104Pro	missense_variant	1/3	1		ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5 linkuse as main transcript	n.310T>C		non_coding_transcript_exon_variant	1/3	1		ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.68e-7

AC:

AN:

1033186

Hom.:

Cov.:

AF XY:

0.00000202

AC XY:

AN XY:

494250

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000931

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

Nov 10, 2021

The c.310T>C (p.S104P) alteration is located in exon 1 (coding exon 1) of the KLF16 gene. This alteration results from a T to C substitution at nucleotide position 310, causing the serine (S) at amino acid position 104 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

0.096

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0042

T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.0041

LIST_S2

Benign

0.27

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.15

N;.

REVEL

Benign

0.025

Sift

Benign

0.23

T;.

Sift4G

Benign

0.30

T;T

Polyphen

0.80

P;P

Vest4

0.18

MutPred

0.29

Loss of phosphorylation at S104 (P = 9e-04);Loss of phosphorylation at S104 (P = 9e-04);

MVP

0.20

MPC

2.0

ClinPred

0.14

GERP RS

1.1

Varity_R

0.15

gMVP

0.35

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