X-150693582-C-T

Variant names:

• chrX-150693582-C-T
• rs1275608657
• NM_001306144.3:c.52C>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.52C>T​(p.Pro18Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000395 in 759,120 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000019 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0000015 (0 hom. 0 hem.)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.22326043).

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>T	p.Pro18Ser	missense	Exon 1 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.52C>T	p.Pro18Ser	missense	Exon 1 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.52C>T	p.Pro18Ser	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>T	p.Pro18Ser	missense	Exon 1 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.52C>T	p.Pro18Ser	missense	Exon 1 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.52C>T	p.Pro18Ser	missense	Exon 1 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes AF: 0.0000185 AC: 2 AN: 107835 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000657

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00000154 AC: 1 AN: 651285 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 196007

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 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: 0.000294 AC: 1 AN: 3400

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 21869

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000185 AC: 2 AN: 107835 Hom.: 0 Cov.: 22 AF XY: 0.0000307 AC XY: 1 AN XY: 32569

African (AFR) AF: 0.0000657 AC: 2 AN: 30454

American (AMR) AF: 0.00 AC: 0 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: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.63	T
M_CAP	Pathogenic	0.80	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Benign	0.76	N
PhyloP100		1.5
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.22
Sift	Benign	0.099	T
Sift4G	Benign	0.73	T
Polyphen		0.016	B
Vest4		0.30
MutPred		0.23		Gain of phosphorylation at P18 (P = 0.0106)
MVP		0.76
ClinPred		0.19	T
GERP RS		1.9
PromoterAI		-0.24	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.048
gMVP		0.32
Mutation Taster		=93/7	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;