chr1-155209231-CC-AG

Variant names:

• chr1-155209231-CC-AG
• NM_002455.5:c.427_428delCCinsAG
• MTX1 p.Pro143Arg

Variant summary

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

The NM_002455.5(MTX1):​c.427_428delCCinsAG​(p.Pro143Arg) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P143L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTX1 NM_002455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

Genes affected

MTX1 (HGNC:7504): (metaxin 1) Predicted to be involved in mitochondrion organization. Part of MIB complex and SAM complex. [provided by Alliance of Genome Resources, Apr 2022]

THBS3 (HGNC:11787): (thrombospondin 3) The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

THBS3 Gene-Disease associations (from GenCC):

• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002455.5. 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
	MTX1	NM_002455.5	MANE Select	c.427_428delCCinsAG	p.Pro143Arg	missense	N/A	NP_002446.3
	MTX1	NM_198883.3		c.427_428delCCinsAG	p.Pro143Arg	missense	N/A	NP_942584.2	Q13505-2
	THBS3	NM_001407556.1		c.-362_-361delGGinsCT		upstream_gene	N/A	NP_001394485.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTX1	ENST00000368376.8	TSL:1 MANE Select	c.427_428delCCinsAG	p.Pro143Arg	missense	N/A	ENSP00000357360.3	Q13505-1
	MTX1	ENST00000316721.8	TSL:1	c.427_428delCCinsAG	p.Pro143Arg	missense	N/A	ENSP00000317106.4	Q13505-2
	MTX1	ENST00000609421.1	TSL:1	c.-21_-20delCCinsAG		upstream_gene	N/A	ENSP00000476632.1	Q13505-3

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		1.8

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: chr1-155179022;