15-31336855-G-A

Variant names:

• chr15-31336855-G-A
• rs66501706
• NM_015995.4:c.577+9066G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015995.4(KLF13):​c.577+9066G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 152,126 control chromosomes in the GnomAD database, including 677 homozygotes. 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 0.073 (677 hom., cov: 32)
• Consequence: KLF13 NM_015995.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 2 publications found

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]

KLF13 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015995.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF13	NM_015995.4	MANE Select	c.577+9066G>A		intron	N/A	NP_057079.2
	KLF13	NM_001302461.2		c.577+9066G>A		intron	N/A	NP_001289390.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF13	ENST00000307145.4	TSL:1 MANE Select	c.577+9066G>A		intron	N/A	ENSP00000302456.3
	KLF13	ENST00000558921.1	TSL:3	n.223+9066G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11096 AN: 152008 Hom.: 676 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.00868

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0320

Gnomad OTH AF: 0.0657

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

GnomAD4 genome AF: 0.0731 AC: 11125 AN: 152126 Hom.: 677 Cov.: 32 AF XY: 0.0724 AC XY: 5384 AN XY: 74384

African (AFR) AF: 0.147 AC: 6095 AN: 41468

American (AMR) AF: 0.116 AC: 1770 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.122 AC: 629 AN: 5176

South Asian (SAS) AF: 0.0284 AC: 137 AN: 4816

European-Finnish (FIN) AF: 0.00868 AC: 92 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0320 AC: 2179 AN: 67992

Other (OTH) AF: 0.0651 AC: 137 AN: 2106

Alfa AF: 0.0421 Hom.: 345

Bravo AF: 0.0846

Asia WGS AF: 0.0780 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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: rs66501706; hg19: chr15-31629058;