10-3781714-C-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001300.6(KLF6):c.603G>A(p.Arg201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,614,124 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0095 (97 hom.)
• Consequence: KLF6 NM_001300.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.591

Genes affected

KLF6 (HGNC:2235): (KLF transcription factor 6) This gene encodes a member of the Kruppel-like family of transcription factors. The zinc finger protein is a transcriptional activator, and functions as a tumor suppressor. Multiple transcript variants encoding different isoforms have been found for this gene, some of which are implicated in carcinogenesis. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 10-3781714-C-T is Benign according to our data. Variant chr10-3781714-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 132786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.591 with no splicing effect.
• BS2: High AC in GnomAd at 1125 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF6	NM_001300.6	c.603G>A	p.Arg201=	synonymous_variant	2/4	ENST00000497571.6
KLF6	NM_001160125.2	c.603G>A	p.Arg201=	synonymous_variant	2/3
KLF6	NM_001160124.2	c.550+53G>A		intron_variant
KLF6	NR_027653.2	n.717+81G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000497571.6	c.603G>A	p.Arg201=	synonymous_variant	2/4	1	NM_001300.6	P1
KLF6	ENST00000469435.1	c.603G>A	p.Arg201=	synonymous_variant	2/2	1
KLF6	ENST00000542957.1	c.603G>A	p.Arg201=	synonymous_variant	2/3	5
KLF6	ENST00000173785.4	n.257+81G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00739 AC: 1125 AN: 152190 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00910

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00769 AC: 1930 AN: 250900 Hom.: 13 AF XY: 0.00783 AC XY: 1062 AN XY: 135686

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00141

Gnomad FIN exome AF: 0.0337

Gnomad NFE exome AF: 0.00906

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.00946 AC: 13824 AN: 1461816 Hom.: 97 Cov.: 32 AF XY: 0.00942 AC XY: 6852 AN XY: 727200

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.00204

Gnomad4 ASJ exome AF: 0.000804

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00159

Gnomad4 FIN exome AF: 0.0306

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00752

GnomAD4 genome AF: 0.00739 AC: 1125 AN: 152308 Hom.: 8 Cov.: 33 AF XY: 0.00831 AC XY: 619 AN XY: 74472

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.00910

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00796 Hom.: 6

Bravo AF: 0.00533

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00871

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	KLF6: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Aug 10, 2018	- -

Hypotension Other:1

not provided, no classification provided

literature only

Centre for molecular medicine, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	7.0
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs112847236; hg19: chr10-3823906; COSMIC: COSV51496375; COSMIC: COSV51496375;