NM_002455.5:c.187T>G

Variant names:

• chr1-155208991-T-G
• rs760077
• NM_002455.5:c.187T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002455.5(MTX1):​c.187T>G​(p.Ser63Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. 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. S63T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTX1 NM_002455.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610
• Publications: 80 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09038597).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTX1	NM_002455.5	MANE Select	c.187T>G	p.Ser63Ala	missense	Exon 1 of 8	NP_002446.3
	MTX1	NM_198883.3		c.187T>G	p.Ser63Ala	missense	Exon 1 of 7	NP_942584.2
	THBS3	NM_001407556.1		c.-121A>C		5_prime_UTR	Exon 1 of 23	NP_001394485.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTX1	ENST00000368376.8	TSL:1 MANE Select	c.187T>G	p.Ser63Ala	missense	Exon 1 of 8	ENSP00000357360.3
	MTX1	ENST00000316721.8	TSL:1	c.187T>G	p.Ser63Ala	missense	Exon 1 of 7	ENSP00000317106.4
	THBS3	ENST00000486260.5	TSL:5	n.61A>C		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_noAF	Benign	-1.0
CADD	Benign	14
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.090	T
PhyloP100		-0.061
Sift4G	Pathogenic	0.0	D
Vest4		0.076
PromoterAI		0.15	Neutral
gMVP		0.12

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

dbSNP: rs760077; hg19: chr1-155178782;