X-150693651-C-A

Position:

• chrX-150693651-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001306144.3(MTMR1):​c.121C>A​(p.Gln41Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 647,675 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 21)
  • Exomes 𝑓: 0.0000062 (0 hom. 0 hem.)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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]

MTMR1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36514974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3	c.121C>A	p.Gln41Lys	missense_variant	1/16	ENST00000445323.7	NP_001293073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR1	ENST00000445323.7	c.121C>A	p.Gln41Lys	missense_variant	1/16	1	NM_001306144.3	ENSP00000414178.2

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 0.00000618 AC: 4 AN: 647675 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 194923

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000678

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 21

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.121C>A (p.Q41K) alteration is located in exon 1 (coding exon 1) of the MTMR1 gene. This alteration results from a C to A substitution at nucleotide position 121, causing the glutamine (Q) at amino acid position 41 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T;.;.;T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.7	L;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.34	N;N;N;N
REVEL	Uncertain	0.55
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.094	B;.;B;B
Vest4		0.39
MutPred		0.19		Gain of ubiquitination at Q41 (P = 0.0022);Gain of ubiquitination at Q41 (P = 0.0022);Gain of ubiquitination at Q41 (P = 0.0022);Gain of ubiquitination at Q41 (P = 0.0022);
MVP		0.99
ClinPred		0.54	D
GERP RS		3.7
Varity_R		0.33
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1444446681; hg19: chrX-149862124;