chr8-102649965-G-A

Position:

• chr8-102649965-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005655.4(KLF10):​c.*167C>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 0.00668 in 749,506 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (113 hom., cov: 33)
  • Exomes 𝑓: 0.0027 (43 hom.)
• Consequence: KLF10 NM_005655.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.909

Genes affected

KLF10 (HGNC:11810): (KLF transcription factor 10) This gene encodes a member of a family of proteins that feature C2H2-type zinc finger domains. The encoded protein is a transcriptional repressor that acts as an effector of transforming growth factor beta signaling. Activity of this protein may inhibit the growth of cancers, particularly pancreatic cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

KLF10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-102649965-G-A is Benign according to our data. Variant chr8-102649965-G-A is described in ClinVar as [Benign]. Clinvar id is 1232719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF10	NM_005655.4	c.*167C>T		3_prime_UTR_variant	4/4	ENST00000285407.11	NP_005646.1
KLF10	NM_001032282.4	c.*167C>T		3_prime_UTR_variant	4/4		NP_001027453.1
KLF10	NR_103759.2	n.935C>T		non_coding_transcript_exon_variant	3/3
KLF10	NR_103760.2	n.1058C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF10	ENST00000285407.11	c.*167C>T		3_prime_UTR_variant	4/4	1	NM_005655.4	ENSP00000285407.6
KLF10	ENST00000395884.3	c.*167C>T		3_prime_UTR_variant	4/4	1		ENSP00000379222.3

Frequencies

GnomAD3 genomes AF: 0.0221 AC: 3356 AN: 152198 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00778

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0167

GnomAD4 exome AF: 0.00274 AC: 1636 AN: 597190 Hom.: 43 Cov.: 8 AF XY: 0.00236 AC XY: 723 AN XY: 306418

Gnomad4 AFR exome AF: 0.0773

Gnomad4 AMR exome AF: 0.00529

Gnomad4 ASJ exome AF: 0.00426

Gnomad4 EAS exome AF: 0.0000316

Gnomad4 SAS exome AF: 0.000317

Gnomad4 FIN exome AF: 0.0000861

Gnomad4 NFE exome AF: 0.000231

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.0222 AC: 3374 AN: 152316 Hom.: 113 Cov.: 33 AF XY: 0.0209 AC XY: 1555 AN XY: 74486

Gnomad4 AFR AF: 0.0768

Gnomad4 AMR AF: 0.00777

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0183 Hom.: 14

Bravo AF: 0.0253

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.75

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: rs75455872; hg19: chr8-103662193;