chr1-44129552-C-T

Variant names:

• chr1-44129552-C-T
• rs2088076591
• NM_173484.4:c.281C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173484.4(KLF17):​c.281C>T​(p.Pro94Leu) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLF17 NM_173484.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0460
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2288951).

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.281C>T	p.Pro94Leu	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.281C>T	p.Pro94Leu	missense	Exon 2 of 4	ENSP00000361373.3	Q5JT82
	KLF17	ENST00000476802.1	TSL:3	n.281C>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000489364.1	A0A0U1RR65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.046
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.045
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.16		Loss of glycosylation at P94 (P = 0.0901)
MVP		0.49
MPC		0.32
ClinPred		0.83	D
GERP RS		2.0
Varity_R		0.10
gMVP		0.62
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs2088076591; hg19: chr1-44595224;