1-173734035-GAG-AAA

Variant names:

• chr1-173734035-GAG-AAA
• NM_014458.4:c.346_348delGAGinsAAA
• KLHL20 p.Glu116Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_014458.4(KLHL20):​c.346_348delGAGinsAAA​(p.Glu116Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E116Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLHL20 NM_014458.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.70
• Publications: 0 publications found

Genes affected

KLHL20 (HGNC:25056): (kelch like family member 20) The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 44-56 amino acid repeat motif. The kelch motif appears in many different polypeptide contexts and contains multiple potential protein-protein contact sites. Members of this family are present both throughout the cell and extracellularly, with diverse activities. [provided by RefSeq, Jul 2008]

KLHL20 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014458.4. 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
	KLHL20	NM_014458.4	MANE Select	c.346_348delGAGinsAAA	p.Glu116Lys	missense	N/A	NP_055273.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL20	ENST00000209884.5	TSL:1 MANE Select	c.346_348delGAGinsAAA	p.Glu116Lys	missense	N/A	ENSP00000209884.4	Q9Y2M5-1
	KLHL20	ENST00000483154.5	TSL:1	n.739_741delGAGinsAAA		non_coding_transcript_exon	Exon 3 of 3
	KLHL20	ENST00000493170.1	TSL:1	n.475_477delGAGinsAAA		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-173703174;