dbSNP rs758567338: KLF17:p.Glu30Lys (chr1-44129359-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_173484.4(KLF17):c.88G>A(p.Glu30Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,358,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

KLF17
NM_173484.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.00700

Publications

4 publications found

Variant links:

Genes affected

KLF17 (HGNC:18830): (KLF transcription factor 17) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to act upstream of or within gamete generation. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

KLF17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06586155).

BP6

Variant 1-44129359-G-A is Benign according to our data. Variant chr1-44129359-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2681354.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173484.4. 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
	KLF17	NM_173484.4	MANE Select	c.88G>A	p.Glu30Lys	missense	Exon 2 of 4	NP_775755.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF17	ENST00000372299.4	TSL:1 MANE Select	c.88G>A	p.Glu30Lys	missense	Exon 2 of 4	ENSP00000361373.3	Q5JT82
	KLF17	ENST00000476802.1	TSL:3	n.88G>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000489364.1	A0A0U1RR65

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000368

AC:

AN:

1358108

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

664054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30064

American (AMR)

AF:

0.00

AC:

AN:

28398

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19802

East Asian (EAS)

AF:

0.00

AC:

AN:

38412

South Asian (SAS)

AF:

0.00

AC:

AN:

68844

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5272

European-Non Finnish (NFE)

AF:

0.00000471

AC:

AN:

1061708

Other (OTH)

AF:

0.00

AC:

AN:

55820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

EBV-positive nodal T- and NK-cell lymphoma (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.5

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.46

M_CAP

Benign

0.0015

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.0

PhyloP100

0.0070

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.97

REVEL

Benign

0.0030

Sift

Benign

0.16

Sift4G

Benign

0.50

Polyphen

0.10

Vest4

0.28

MutPred

0.31

Gain of ubiquitination at E30 (P = 0.0022)

MVP

0.25

MPC

0.095

ClinPred

0.077

GERP RS

0.72

Varity_R

0.036

gMVP

0.36

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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