10-3779477-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_001300.6(KLF6):c.*62G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00299 in 1,419,224 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.014 (63 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (52 hom.)
• Consequence: KLF6 NM_001300.6 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.74

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0144 (2195/152318) while in subpopulation AFR AF= 0.0496 (2059/41552). AF 95% confidence interval is 0.0478. There are 63 homozygotes in gnomad4. There are 1002 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High AC in GnomAd at 2182 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLF6	NM_001300.6	c.*62G>A		3_prime_UTR_variant	4/4	ENST00000497571.6
KLF6	NM_001160124.2	c.*62G>A		3_prime_UTR_variant	4/4
KLF6	NM_001160125.2	c.*76G>A		3_prime_UTR_variant	3/3
KLF6	NR_027653.2	n.955G>A		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF6	ENST00000497571.6	c.*62G>A		3_prime_UTR_variant	4/4	1	NM_001300.6	P1
KLF6	ENST00000542957.1	c.*76G>A		3_prime_UTR_variant	3/3	5
KLF6	ENST00000173785.4	n.495G>A		non_coding_transcript_exon_variant	3/3	2
KLF6	ENST00000461124.1	n.226G>A		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2182 AN: 152200 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00391 AC: 972 AN: 248806 Hom.: 19 AF XY: 0.00293 AC XY: 394 AN XY: 134648

Gnomad AFR exome AF: 0.0507

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000214

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00162 AC: 2054 AN: 1266906 Hom.: 52 Cov.: 18 AF XY: 0.00140 AC XY: 894 AN XY: 639846

Gnomad4 AFR exome AF: 0.0510

Gnomad4 AMR exome AF: 0.00384

Gnomad4 ASJ exome AF: 0.0000402

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000170

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.00411

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152318 Hom.: 63 Cov.: 33 AF XY: 0.0135 AC XY: 1002 AN XY: 74484

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.00614

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00839 Hom.: 4

Bravo AF: 0.0155

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

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	-0.54
Cadd	Benign	21
Dann	Benign	0.83

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: rs112418040; hg19: chr10-3821669;