7-130733352-C-T

Variant names:

• chr7-130733352-C-T
• rs1554470857
• NM_138693.4:c.682G>A

Variant summary

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

The NM_138693.4(KLF14):​c.682G>A​(p.Asp228Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: KLF14 NM_138693.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00300
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1241861).

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.682G>A	p.Asp228Asn	missense	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.682G>A	p.Asp228Asn	missense	Exon 1 of 1	ENSP00000463287.1	Q8TD94

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461596 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727084

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 32

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	Pathogenic	0.60
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.33	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.98	L
PhyloP100		0.0030
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.29	T
Polyphen		0.82	P
Vest4		0.16
MutPred		0.25		Loss of stability (P = 0.0587)
MVP		0.099
ClinPred		0.88	D
GERP RS		2.3
Varity_R		0.082
gMVP		0.43
Mutation Taster		=99/1	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: rs1554470857; hg19: chr7-130418179;