chr2-10053051-C-G

Variant names:

• chr2-10053051-C-G
• rs4444493
• NM_003597.5:c.*544C>G

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.*544C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000832 in 240,348 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: 0.0000083 (0 hom.)
• Consequence: KLF11 NM_003597.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• 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

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=-0.82).

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.*544C>G		3_prime_UTR	Exon 4 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.*544C>G		3_prime_UTR	Exon 4 of 4	NP_001171187.1	O14901-2
	KLF11	NM_001177718.2		c.*544C>G		3_prime_UTR	Exon 4 of 4	NP_001171189.1	O14901-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.*544C>G		3_prime_UTR	Exon 4 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000535335.1	TSL:2	c.*544C>G		3_prime_UTR	Exon 4 of 4	ENSP00000442722.1	O14901-2
	KLF11	ENST00000540845.5	TSL:2	c.*544C>G		3_prime_UTR	Exon 4 of 4	ENSP00000444690.1	O14901-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000832 AC: 2 AN: 240348 Hom.: 0 Cov.: 0 AF XY: 0.00000820 AC XY: 1 AN XY: 121904

African (AFR) AF: 0.00 AC: 0 AN: 7028

American (AMR) AF: 0.00 AC: 0 AN: 7330

Ashkenazi Jewish (ASJ) AF: 0.000110 AC: 1 AN: 9056

East Asian (EAS) AF: 0.00 AC: 0 AN: 22442

South Asian (SAS) AF: 0.00 AC: 0 AN: 2186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1248

European-Non Finnish (NFE) AF: 0.00000645 AC: 1 AN: 155028

Other (OTH) AF: 0.00 AC: 0 AN: 15994

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4444493; hg19: chr2-10193178;