10-3777522-C-T

Variant names:

• chr10-3777522-C-T
• rs1043009
• NM_001300.6:c.*2017G>A

Variant summary

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

The NM_001300.6(KLF6):​c.*2017G>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 0.33 in 511,580 control chromosomes in the GnomAD database, including 30,959 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 0.27 (7268 hom., cov: 31)
  • Exomes 𝑓: 0.35 (23691 hom.)
• Consequence: KLF6 NM_001300.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.846
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	NM_001300.6	MANE Select	c.*2017G>A		3_prime_UTR	Exon 4 of 4	NP_001291.3
	KLF6	NM_001160124.2		c.*2017G>A		3_prime_UTR	Exon 4 of 4	NP_001153596.1	D3GC14
	KLF6	NM_001160125.2		c.*2031G>A		3_prime_UTR	Exon 3 of 3	NP_001153597.1	Q99612-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	ENST00000497571.6	TSL:1 MANE Select	c.*2017G>A		3_prime_UTR	Exon 4 of 4	ENSP00000419923.1	Q99612-1
	KLF6	ENST00000542957.1	TSL:5	c.*2031G>A		3_prime_UTR	Exon 3 of 3	ENSP00000445301.1	Q99612-3
	KLF6	ENST00000461124.1	TSL:5	n.357-1119G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41799 AN: 151852 Hom.: 7273 Cov.: 31

Gnomad AFR AF: 0.0680

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.335 AC: 43768 AN: 130470 AF XY: 0.343

Gnomad AFR exome AF: 0.0567

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.478

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.354

GnomAD4 exome AF: 0.353 AC: 126907 AN: 359608 Hom.: 23691 Cov.: 0 AF XY: 0.358 AC XY: 71133 AN XY: 198722

African (AFR) AF: 0.0599 AC: 668 AN: 11146

American (AMR) AF: 0.262 AC: 7584 AN: 28908

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 4839 AN: 14516

East Asian (EAS) AF: 0.507 AC: 9144 AN: 18036

South Asian (SAS) AF: 0.353 AC: 21220 AN: 60168

European-Finnish (FIN) AF: 0.267 AC: 3316 AN: 12404

Middle Eastern (MID) AF: 0.378 AC: 570 AN: 1506

European-Non Finnish (NFE) AF: 0.378 AC: 73356 AN: 194110

Other (OTH) AF: 0.330 AC: 6210 AN: 18814

GnomAD4 genome AF: 0.275 AC: 41784 AN: 151972 Hom.: 7268 Cov.: 31 AF XY: 0.270 AC XY: 20081 AN XY: 74280

African (AFR) AF: 0.0678 AC: 2810 AN: 41476

American (AMR) AF: 0.266 AC: 4063 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2587 AN: 5164

South Asian (SAS) AF: 0.335 AC: 1613 AN: 4814

European-Finnish (FIN) AF: 0.258 AC: 2712 AN: 10520

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25723 AN: 67946

Other (OTH) AF: 0.279 AC: 591 AN: 2116

Alfa AF: 0.334 Hom.: 4094

Bravo AF: 0.267

Asia WGS AF: 0.336 AC: 1165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.3
DANN	Benign	0.72
PhyloP100		0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1043009; hg19: chr10-3819714; COSMIC: COSV51494114; COSMIC: COSV51494114;