10-3779369-G-A

Variant names:

• chr10-3779369-G-A
• rs17731
• NM_001300.6:c.*170C>T

Variant summary

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

The NM_001300.6(KLF6):​c.*170C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 697,650 control chromosomes in the GnomAD database, including 43,348 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 (7164 hom., cov: 32)
  • Exomes 𝑓: 0.35 (36184 hom.)
• Consequence: KLF6 NM_001300.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 18 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=-0.56).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	NM_001300.6	MANE Select	c.*170C>T		3_prime_UTR	Exon 4 of 4	NP_001291.3
	KLF6	NR_027653.2		n.1063C>T		non_coding_transcript_exon	Exon 4 of 4
	KLF6	NM_001160124.2		c.*170C>T		3_prime_UTR	Exon 4 of 4	NP_001153596.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF6	ENST00000497571.6	TSL:1 MANE Select	c.*170C>T		3_prime_UTR	Exon 4 of 4	ENSP00000419923.1
	KLF6	ENST00000173785.4	TSL:2	n.603C>T		non_coding_transcript_exon	Exon 3 of 3
	KLF6	ENST00000461124.1	TSL:5	n.334C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41682 AN: 151972 Hom.: 7169 Cov.: 32

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.282

GnomAD2 exomes AF: 0.334 AC: 46496 AN: 139352 AF XY: 0.341

Gnomad AFR exome AF: 0.0628

Gnomad AMR exome AF: 0.264

Gnomad ASJ exome AF: 0.336

Gnomad EAS exome AF: 0.476

Gnomad FIN exome AF: 0.259

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.355 AC: 193428 AN: 545560 Hom.: 36184 Cov.: 5 AF XY: 0.358 AC XY: 105563 AN XY: 294840

African (AFR) AF: 0.0697 AC: 1085 AN: 15562

American (AMR) AF: 0.261 AC: 8952 AN: 34238

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 6611 AN: 19758

East Asian (EAS) AF: 0.516 AC: 16240 AN: 31502

South Asian (SAS) AF: 0.351 AC: 21748 AN: 61938

European-Finnish (FIN) AF: 0.266 AC: 9442 AN: 35538

Middle Eastern (MID) AF: 0.368 AC: 887 AN: 2410

European-Non Finnish (NFE) AF: 0.377 AC: 118682 AN: 314804

Other (OTH) AF: 0.328 AC: 9781 AN: 29810

GnomAD4 genome AF: 0.274 AC: 41666 AN: 152090 Hom.: 7164 Cov.: 32 AF XY: 0.270 AC XY: 20054 AN XY: 74352

African (AFR) AF: 0.0728 AC: 3023 AN: 41526

American (AMR) AF: 0.264 AC: 4034 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1189 AN: 3468

East Asian (EAS) AF: 0.501 AC: 2577 AN: 5142

South Asian (SAS) AF: 0.334 AC: 1611 AN: 4822

European-Finnish (FIN) AF: 0.257 AC: 2720 AN: 10576

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25457 AN: 67954

Other (OTH) AF: 0.279 AC: 590 AN: 2112

Alfa AF: 0.320 Hom.: 6303

Bravo AF: 0.266

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs17731; hg19: chr10-3821561; COSMIC: COSV51494121; COSMIC: COSV51494121;