X-56265385-C-A

Position:

• chrX-56265385-C-A

Variant summary

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

The NM_007250.5(KLF8):​c.287C>A​(p.Ala96Asp) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: KLF8 NM_007250.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.433

Genes affected

KLF8 (HGNC:6351): (KLF transcription factor 8) This gene encodes a protein which is a member of the Sp/KLF family of transcription factors. Members of this family contain a C-terminal DNA-binding domain with three Kruppel-like zinc fingers. The encoded protein is thought to play an important role in the regulation of epithelial to mesenchymal transition, a process which occurs normally during development but also during metastasis. A pseudogene has been identified on chromosome 16. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

KLF8 (HGNC:):

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=0.12698162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF8	NM_007250.5	c.287C>A	p.Ala96Asp	missense_variant	3/6	ENST00000468660.6	NP_009181.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF8	ENST00000468660.6	c.287C>A	p.Ala96Asp	missense_variant	3/6	1	NM_007250.5	ENSP00000417303.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.287C>A (p.A96D) alteration is located in exon 3 (coding exon 3) of the KLF8 gene. This alteration results from a C to A substitution at nucleotide position 287, causing the alanine (A) at amino acid position 96 to be replaced by an aspartic acid (D). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	.;T;.
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.72	T;T;T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	N;N;.
REVEL	Benign	0.077
Sift	Uncertain	0.0060	D;D;.
Sift4G	Benign	0.065	T;T;.
Polyphen		0.23	.;B;.
Vest4		0.16
MutPred		0.11		Loss of methylation at K95 (P = 0.1186);Loss of methylation at K95 (P = 0.1186);.;
MVP		0.91
MPC		0.15
ClinPred		0.74	D
GERP RS		2.9
Varity_R		0.56
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-56291818;