15-31327495-C-T

Position:

• chr15-31327495-C-T

Variant summary

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

The NM_015995.4(KLF13):​c.283C>T​(p.Pro95Ser) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLF13 NM_015995.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.672

Genes affected

KLF13 (HGNC:13672): (KLF transcription factor 13) KLF13 belongs to a family of transcription factors that contain 3 classical zinc finger DNA-binding domains consisting of a zinc atom tetrahedrally coordinated by 2 cysteines and 2 histidines (C2H2 motif). These transcription factors bind to GC-rich sequences and related GT and CACCC boxes (Scohy et al., 2000 [PubMed 11087666]).[supplied by OMIM, Mar 2008]

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=0.15663436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF13	NM_015995.4	c.283C>T	p.Pro95Ser	missense_variant	1/2	ENST00000307145.4	NP_057079.2
KLF13	NM_001302461.2	c.283C>T	p.Pro95Ser	missense_variant	1/2		NP_001289390.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF13	ENST00000307145.4	c.283C>T	p.Pro95Ser	missense_variant	1/2	1	NM_015995.4	ENSP00000302456.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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

Feb 05, 2024

The c.283C>T (p.P95S) alteration is located in exon 1 (coding exon 1) of the KLF13 gene. This alteration results from a C to T substitution at nucleotide position 283, causing the proline (P) at amino acid position 95 to be replaced by a serine (S). 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	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.043
Sift	Benign	0.21	T
Sift4G	Benign	0.44	T
Polyphen		0.97	D
Vest4		0.11
MutPred		0.26		Loss of catalytic residue at P95 (P = 0.002);
MVP		0.15
MPC		2.1
ClinPred		0.54	D
GERP RS		2.3
Varity_R		0.069
gMVP		0.28

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: rs1030560832; hg19: chr15-31619698;