chr20-36793255-GGG-TGT

Variant names:

• chr20-36793255-GGG-TGT
• NM_080627.4:c.4825_4827delCCCinsACA
• MTCL2 p.Pro1609Thr

Variant summary

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

The NM_080627.4(MTCL2):​c.4825_4827delCCCinsACA​(p.Pro1609Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTCL2 NM_080627.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 0 publications found

Genes affected

MTCL2 (HGNC:16111): (microtubule crosslinking factor 2) Predicted to be involved in insulin receptor signaling pathway; negative regulation of gluconeogenesis; and regulation of autophagy. Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080627.4. 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
	MTCL2	NM_080627.4	MANE Select	c.4825_4827delCCCinsACA	p.Pro1609Thr	missense	N/A	NP_542194.2	O94964-2
	MTCL2	NM_199181.3		c.2993+1118_2993+1120delCCCinsACA		intron	N/A	NP_954650.2	X6R3R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTCL2	ENST00000237536.9	TSL:5 MANE Select	c.4825_4827delCCCinsACA	p.Pro1609Thr	missense	N/A	ENSP00000237536.4	O94964-2
	MTCL2	ENST00000938705.1		c.4762_4764delCCCinsACA	p.Pro1588Thr	missense	N/A	ENSP00000608764.1
	MTCL2	ENST00000279034.10	TSL:5	c.2993+1118_2993+1120delCCCinsACA		intron	N/A	ENSP00000279034.5	X6R3R3

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		2.9

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: chr20-35421658;