17-76733367-CAA-GAG

Variant names:

• chr17-76733367-CAA-GAG
• NM_001080510.5:c.397_399delCAAinsGAG
• METTL23 p.Gln133Glu

Variant summary

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

The NM_001080510.5(METTL23):​c.397_399delCAAinsGAG​(p.Gln133Glu) 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: METTL23 NM_001080510.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.94
• Publications: 0 publications found

Genes affected

METTL23 (HGNC:26988): (methyltransferase 23, arginine) The protein encoded by this gene functions as a transcription factor regulator in the transcriptional pathway for human cognition. It is a partner of the alpha subunit of the GA-binding protein transcription factor. Mutations in this gene cause mild autosomal recessive intellectual disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

METTL23 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 44

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000267168 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080510.5. 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
	METTL23	NM_001080510.5	MANE Select	c.397_399delCAAinsGAG	p.Gln133Glu	missense	N/A	NP_001073979.3	Q86XA0-1
	METTL23	NM_001206983.3		c.397_399delCAAinsGAG	p.Gln133Glu	missense	N/A	NP_001193912.1	Q86XA0-1
	METTL23	NM_001206984.3		c.397_399delCAAinsGAG	p.Gln133Glu	missense	N/A	NP_001193913.1	Q86XA0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	METTL23	ENST00000341249.11	TSL:1 MANE Select	c.397_399delCAAinsGAG	p.Gln133Glu	missense	N/A	ENSP00000341543.5	Q86XA0-1
	METTL23	ENST00000590964.5	TSL:1	c.196_198delCAAinsGAG	p.Gln66Glu	missense	N/A	ENSP00000465890.1	Q86XA0-2
	METTL23	ENST00000586200.1	TSL:1	c.40_42delCAAinsGAG	p.Gln14Glu	missense	N/A	ENSP00000465959.1	K7EL83

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9

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: chr17-74729449;