15-31327239-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_015995.4(KLF13):c.27C>T(p.His9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 1,377,540 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (33 hom.)
• Consequence: KLF13 NM_015995.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.02

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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 15-31327239-C-T is Benign according to our data. Variant chr15-31327239-C-T is described in ClinVar as [Benign]. Clinvar id is 715460.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.02 with no splicing effect.
• BS2: High AC in GnomAd at 809 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF13	NM_015995.4	c.27C>T	p.His9=	synonymous_variant	1/2	ENST00000307145.4
KLF13	NM_001302461.2	c.27C>T	p.His9=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF13	ENST00000307145.4	c.27C>T	p.His9=	synonymous_variant	1/2	1	NM_015995.4	P1

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 809 AN: 150374 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00311

Gnomad ASJ AF: 0.00232

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.0261

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00625

Gnomad OTH AF: 0.00580

GnomAD3 exomes AF: 0.00514 AC: 247 AN: 48056 Hom.: 6 AF XY: 0.00453 AC XY: 130 AN XY: 28666

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00477

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00265

Gnomad FIN exome AF: 0.0215

Gnomad NFE exome AF: 0.00576

Gnomad OTH exome AF: 0.00408

GnomAD4 exome AF: 0.00576 AC: 7068 AN: 1227058 Hom.: 33 Cov.: 33 AF XY: 0.00570 AC XY: 3447 AN XY: 604240

Gnomad4 AFR exome AF: 0.000670

Gnomad4 AMR exome AF: 0.00254

Gnomad4 ASJ exome AF: 0.00437

Gnomad4 EAS exome AF: 0.0000391

Gnomad4 SAS exome AF: 0.00247

Gnomad4 FIN exome AF: 0.0254

Gnomad4 NFE exome AF: 0.00577

Gnomad4 OTH exome AF: 0.00506

GnomAD4 genome AF: 0.00537 AC: 808 AN: 150482 Hom.: 11 Cov.: 32 AF XY: 0.00644 AC XY: 473 AN XY: 73496

Gnomad4 AFR AF: 0.00128

Gnomad4 AMR AF: 0.00304

Gnomad4 ASJ AF: 0.00232

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.0261

Gnomad4 NFE AF: 0.00625

Gnomad4 OTH AF: 0.00574

Alfa AF: 0.00884 Hom.: 3

Bravo AF: 0.00324

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	13
Dann	Uncertain	0.98

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: rs77996726; hg19: chr15-31619442; COSMIC: COSV56147144; COSMIC: COSV56147144;