chrX-150718695-C-T

Variant names:

• chrX-150718695-C-T
• NM_001306144.3:c.347C>T

Variant summary

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

The NM_001306144.3(MTMR1):​c.347C>T​(p.Ala116Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000948 in 1,054,870 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.85
• 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: 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=0.19032374).

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.347C>T	p.Ala116Val	missense	Exon 4 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.374C>T	p.Ala125Val	missense	Exon 4 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.323C>T	p.Ala108Val	missense	Exon 3 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.347C>T	p.Ala116Val	missense	Exon 4 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.323C>T	p.Ala108Val	missense	Exon 3 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.323C>T	p.Ala108Val	missense	Exon 3 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD4 exome AF: 9.48e-7 AC: 1 AN: 1054870 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 340470

African (AFR) AF: 0.00 AC: 0 AN: 24679

American (AMR) AF: 0.00 AC: 0 AN: 32792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17359

East Asian (EAS) AF: 0.00 AC: 0 AN: 27906

South Asian (SAS) AF: 0.00 AC: 0 AN: 52408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37287

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3838

European-Non Finnish (NFE) AF: 0.00000123 AC: 1 AN: 815565

Other (OTH) AF: 0.00 AC: 0 AN: 43036

GnomAD4 genome Cov.: 19

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	Benign	0.16
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Uncertain	0.52	D
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	0.17	N
PhyloP100		3.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.24
Sift	Benign	0.51	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.51		Gain of ubiquitination at K115 (P = 0.1064)
MVP		0.76
ClinPred		0.27	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.68
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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-149887167;