X-150731555-C-T

Variant names:

• chrX-150731555-C-T
• NM_001306144.3:c.827C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001306144.3(MTMR1):​c.827C>T​(p.Pro276Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.84
• Publications: 0 publications found

Genes affected

MTMR1 (HGNC:7449): (myotubularin related protein 1) This gene encodes a member of the myotubularin related family of proteins. Members of this family contain the consensus sequence for the active site of protein tyrosine phosphatases. Alternatively spliced variants have been described but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.995

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306144.3. 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
	MTMR1	NM_001306144.3	MANE Select	c.827C>T	p.Pro276Leu	missense	Exon 9 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.854C>T	p.Pro285Leu	missense	Exon 9 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.803C>T	p.Pro268Leu	missense	Exon 8 of 16	NP_003819.1	Q13613-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR1	ENST00000445323.7	TSL:1 MANE Select	c.827C>T	p.Pro276Leu	missense	Exon 9 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.803C>T	p.Pro268Leu	missense	Exon 8 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.803C>T	p.Pro268Leu	missense	Exon 8 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.74	D
BayesDel_noAF	Pathogenic	0.82
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.98	D
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.91	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		7.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Pathogenic	-9.6	D
REVEL	Pathogenic	0.99
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.92		Loss of ubiquitination at K280 (P = 0.0699)
MVP		1.0
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.96
gMVP		0.96
Mutation Taster		=5/95	disease causing

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

hg19: chrX-149900027;