Genetic Variant KLF16:p.Ala73Ser (chr19-1863281-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031918.4(KLF16):c.217G>T(p.Ala73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: 0.432

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045170426).

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.217G>T	p.Ala73Ser	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.217G>T	p.Ala73Ser	missense	Exon 1 of 2	ENSP00000250916.3	Q9BXK1
KLF16	ENST00000617223.1	TSL:1	c.217G>T	p.Ala73Ser	missense	Exon 1 of 3	ENSP00000483701.1	Q9BXK1
KLF16	ENST00000541015.5	TSL:1	n.217G>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000439973.1	Q9BXK1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

842194

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

389974

African (AFR)

AF:

0.00

AC:

AN:

15928

American (AMR)

AF:

0.00

AC:

AN:

1280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5384

East Asian (EAS)

AF:

0.00

AC:

AN:

3910

South Asian (SAS)

AF:

0.00

AC:

AN:

17348

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1098

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1666

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

767752

Other (OTH)

AF:

0.00

AC:

AN:

27828

GnomAD4 genome

Cov.:

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

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.4

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.31

M_CAP

Benign

0.0047

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.0

PhyloP100

0.43

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.0

REVEL

Benign

0.034

Sift

Benign

0.99

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.075

MutPred

0.25

Gain of glycosylation at A73 (P = 0.0019)

MVP

0.14

MPC

1.2

ClinPred

0.064

GERP RS

-0.66

PromoterAI

0.017

Neutral

(source)

Varity_R

0.031

gMVP

0.25

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over