NM_003597.5:c.36G>A

Variant names:

• chr2-10043752-G-A
• NM_003597.5:c.36G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003597.5(KLF11):​c.36G>A​(p.Ala12Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000812 in 1,231,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: KLF11 NM_003597.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.485
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 2-10043752-G-A is Benign according to our data. Variant chr2-10043752-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2018955.Status of the report is criteria_provided_single_submitter, 1 stars.

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.36G>A	p.Ala12Ala	synonymous	Exon 1 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.-145G>A		upstream_gene	N/A	NP_001171187.1	O14901-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000921466.1		c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 3	ENSP00000591525.1
	KLF11	ENST00000401510.5	TSL:3	c.-10+681G>A		intron	N/A	ENSP00000386058.1	B5MCC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.12e-7 AC: 1 AN: 1231548 Hom.: 0 Cov.: 29 AF XY: 0.00000164 AC XY: 1 AN XY: 608056

African (AFR) AF: 0.00 AC: 0 AN: 23910

American (AMR) AF: 0.00 AC: 0 AN: 28058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19210

East Asian (EAS) AF: 0.00 AC: 0 AN: 21748

South Asian (SAS) AF: 0.00 AC: 0 AN: 74076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28444

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3730

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 984740

Other (OTH) AF: 0.00 AC: 0 AN: 47632

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		0.48
PromoterAI		-0.10	Neutral
Mutation Taster		=100/0	polymorphism

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

hg19: chr2-10183879;