7-130733127-C-A

Variant names:

• chr7-130733127-C-A
• rs781966832
• NM_138693.4:c.907G>T

Variant summary

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

The NM_138693.4(KLF14):​c.907G>T​(p.Glu303*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,440,594 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (1 hom.)
• Consequence: KLF14 NM_138693.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.90
• Publications: 0 publications found

Genes affected

KLF14 (HGNC:23025): (KLF transcription factor 14) This intronless gene encodes a member of the Kruppel-like family of transcription factors. The encoded protein functions as a transcriptional co-repressor, and is induced by transforming growth factor-beta (TGF-beta) to repress TGF-beta receptor II gene expression. This gene exhibits imprinted expression from the maternal allele in embryonic and extra-embryonic tissues. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138693.4. 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
	KLF14	NM_138693.4	MANE Select	c.907G>T	p.Glu303*	stop_gained	Exon 1 of 1	NP_619638.2	Q8TD94

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF14	ENST00000583337.4	TSL:6 MANE Select	c.907G>T	p.Glu303*	stop_gained	Exon 1 of 1	ENSP00000463287.1	Q8TD94

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000132 AC: 3 AN: 227370 AF XY: 0.0000245

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000113

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1440594 Hom.: 1 Cov.: 30 AF XY: 0.00000981 AC XY: 7 AN XY: 713626

African (AFR) AF: 0.00 AC: 0 AN: 33212

American (AMR) AF: 0.00 AC: 0 AN: 42318

Ashkenazi Jewish (ASJ) AF: 0.0000399 AC: 1 AN: 25080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39186

South Asian (SAS) AF: 0.0000721 AC: 6 AN: 83254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099898

Other (OTH) AF: 0.00 AC: 0 AN: 59518

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	32
DANN	Benign	0.93
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.12	N
PhyloP100		-1.9
Vest4		0.71
GERP RS		1.1
Mutation Taster		=175/25	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: rs781966832; hg19: chr7-130417954;