1-44129735-C-T

Variant names:

• chr1-44129735-C-T
• rs777651690
• NM_173484.4:c.464C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173484.4(KLF17):​c.464C>T​(p.Pro155Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P155R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLF17 NM_173484.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.516

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

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=0.09606972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF17	NM_173484.4	c.464C>T	p.Pro155Leu	missense_variant	Exon 2 of 4	ENST00000372299.4	NP_775755.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF17	ENST00000372299.4	c.464C>T	p.Pro155Leu	missense_variant	Exon 2 of 4	1	NM_173484.4	ENSP00000361373.3
KLF17	ENST00000476802.1	n.289+175C>T		intron_variant	Intron 2 of 3	3		ENSP00000489364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.13
DANN	Benign	0.54
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.081
Sift	Benign	0.47	T
Sift4G	Benign	0.14	T
Polyphen		0.0030	B
Vest4		0.072
MutPred		0.52		Loss of catalytic residue at P154 (P = 0.0191);
MVP		0.30
MPC		0.084
ClinPred		0.046	T
GERP RS		-2.0
Varity_R		0.023
gMVP		0.24

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

Other links and lift over

dbSNP: rs777651690; hg19: chr1-44595407;