chrX-56125254-A-T

Position:

• chrX-56125254-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001324104.1(KLF8):​c.22+110293A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00956 in 111,804 control chromosomes in the GnomAD database, including 9 homozygotes. There are 300 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0096 (9 hom., 300 hem., cov: 23)
• Consequence: KLF8 NM_001324104.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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]

LOC124900486 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00956 (1069/111804) while in subpopulation SAS AF= 0.0313 (83/2653). AF 95% confidence interval is 0.0259. There are 9 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF8	NM_001324104.1	c.22+110293A>T		intron_variant			NP_001311033.1
KLF8	NM_001324105.1	c.-2-124977A>T		intron_variant			NP_001311034.1
LOC124900486	XR_007068244.1	n.17836A>T		non_coding_transcript_exon_variant	1/2
LOC124900486	XR_007068245.1	n.597+70173A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000227486	ENST00000655874.1	n.353-79719A>T		intron_variant
ENSG00000227486	ENST00000661602.1	n.1010-79719A>T		intron_variant
ENSG00000227486	ENST00000669152.2	n.676-79719A>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00957 AC: 1069 AN: 111755 Hom.: 9 Cov.: 23 AF XY: 0.00884 AC XY: 300 AN XY: 33937

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00970

Gnomad ASJ AF: 0.0155

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0208

Gnomad NFE AF: 0.0140

Gnomad OTH AF: 0.0146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00956 AC: 1069 AN: 111804 Hom.: 9 Cov.: 23 AF XY: 0.00882 AC XY: 300 AN XY: 33996

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00969

Gnomad4 ASJ AF: 0.0155

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0313

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.0140

Gnomad4 OTH AF: 0.0145

Alfa AF: 0.0111 Hom.: 58

Bravo AF: 0.00902

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.62
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10521482; hg19: chrX-56151687;