X-150693651-C-A

Variant names:

• chrX-150693651-C-A
• rs1444446681
• NM_001306144.3:c.121C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 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 1 ACMG points.

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

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.121C>A	p.Gln41Lys	missense	Exon 1 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.121C>A	p.Gln41Lys	missense	Exon 1 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.121C>A	p.Gln41Lys	missense	Exon 1 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.121C>A	p.Gln41Lys	missense	Exon 1 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.121C>A	p.Gln41Lys	missense	Exon 1 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.121C>A	p.Gln41Lys	missense	Exon 1 of 10	ENSP00000445281.1	Q8NEC6

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

African (AFR) AF: 0.00 AC: 0 AN: 12535

American (AMR) AF: 0.00 AC: 0 AN: 1071

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4138

East Asian (EAS) AF: 0.00 AC: 0 AN: 3249

South Asian (SAS) AF: 0.00 AC: 0 AN: 12677

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1128

European-Non Finnish (NFE) AF: 0.00000678 AC: 4 AN: 590184

Other (OTH) AF: 0.00 AC: 0 AN: 21599

GnomAD4 genome Cov.: 21

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.23
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.76	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Benign	0.37	T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.7	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.34	N
REVEL	Uncertain	0.55
Sift	Benign	1.0	T
Sift4G	Benign	0.54	T
Polyphen		0.094	B
Vest4		0.39
MutPred		0.19		Gain of ubiquitination at Q41 (P = 0.0022)
MVP		0.99
ClinPred		0.54	D
GERP RS		3.7
PromoterAI		0.23	Neutral
Varity_R		0.33
gMVP		0.33
Mutation Taster		=78/22	polymorphism

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: rs1444446681; hg19: chrX-149862124;