X-150693582-C-G

Variant names:

• chrX-150693582-C-G
• rs1275608657
• NM_001306144.3:c.52C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001306144.3(MTMR1):​c.52C>G​(p.Pro18Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000408 in 759,120 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.000017 (0 hom. 1 hem.)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• 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_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18558523).
• BS2: High Hemizygotes in GnomAd4 at 6 gene

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.52C>G	p.Pro18Ala	missense	Exon 1 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.52C>G	p.Pro18Ala	missense	Exon 1 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.52C>G	p.Pro18Ala	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.52C>G	p.Pro18Ala	missense	Exon 1 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.52C>G	p.Pro18Ala	missense	Exon 1 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.52C>G	p.Pro18Ala	missense	Exon 1 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 20 AN: 107835 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000591

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000169 AC: 11 AN: 651285 Hom.: 0 Cov.: 25 AF XY: 0.00000510 AC XY: 1 AN XY: 196007

African (AFR) AF: 0.000397 AC: 5 AN: 12605

American (AMR) AF: 0.00 AC: 0 AN: 1195

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4247

East Asian (EAS) AF: 0.00 AC: 0 AN: 3400

South Asian (SAS) AF: 0.0000787 AC: 1 AN: 12705

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1611

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 592505

Other (OTH) AF: 0.000229 AC: 5 AN: 21869

GnomAD4 genome AF: 0.000185 AC: 20 AN: 107835 Hom.: 0 Cov.: 22 AF XY: 0.000184 AC XY: 6 AN XY: 32569

African (AFR) AF: 0.000591 AC: 18 AN: 30454

American (AMR) AF: 0.000191 AC: 2 AN: 10466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2578

East Asian (EAS) AF: 0.00 AC: 0 AN: 3416

South Asian (SAS) AF: 0.00 AC: 0 AN: 2746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51315

Other (OTH) AF: 0.00 AC: 0 AN: 1469

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000166

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	0.053
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.76	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.41	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.29
Sift	Benign	0.18	T
Sift4G	Benign	0.68	T
Polyphen		0.0030	B
Vest4		0.32
MutPred		0.15		Loss of glycosylation at P20 (P = 0.1311)
MVP		0.82
ClinPred		0.051	T
GERP RS		1.9
PromoterAI		-0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.048
gMVP		0.27
Mutation Taster		=94/6	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: rs1275608657; hg19: chrX-149862055;