2-10043708-G-T

Variant names:

• chr2-10043708-G-T
• rs550497503
• NM_003597.5:c.-9G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003597.5(KLF11):​c.-9G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,205,436 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: KLF11 NM_003597.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.221
• Publications: 0 publications found

Genes affected

KLF11 (HGNC:11811): (KLF transcription factor 11) The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

KLF11 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 7

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000260077 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003597.5. 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
	KLF11	NM_003597.5	MANE Select	c.-9G>T		5_prime_UTR	Exon 1 of 4	NP_003588.1
	KLF11	NM_001177716.2		c.-189G>T		upstream_gene	N/A	NP_001171187.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.-9G>T		5_prime_UTR	Exon 1 of 4	ENSP00000307023.1
	KLF11	ENST00000921466.1		c.-9G>T		5_prime_UTR	Exon 1 of 3	ENSP00000591525.1
	KLF11	ENST00000401510.5	TSL:3	c.-10+637G>T		intron	N/A	ENSP00000386058.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1205436 Hom.: 0 Cov.: 29 AF XY: 0.00000168 AC XY: 1 AN XY: 594936

African (AFR) AF: 0.00 AC: 0 AN: 23096

American (AMR) AF: 0.00 AC: 0 AN: 26426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18438

East Asian (EAS) AF: 0.00 AC: 0 AN: 19106

South Asian (SAS) AF: 0.00 AC: 0 AN: 72650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3360

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 970554

Other (OTH) AF: 0.00 AC: 0 AN: 46020

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.89
PhyloP100		-0.22
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs550497503; hg19: chr2-10183835;