X-150693596-G-A

Variant names:

• chrX-150693596-G-A
• rs1295395837
• NM_001306144.3:c.66G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001306144.3(MTMR1):​c.66G>A​(p.Pro22Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 107,650 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P22P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000093 (0 hom., 1 hem., cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MTMR1 NM_001306144.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.145 with no splicing effect.

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.66G>A	p.Pro22Pro	synonymous	Exon 1 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.66G>A	p.Pro22Pro	synonymous	Exon 1 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.66G>A	p.Pro22Pro	synonymous	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.66G>A	p.Pro22Pro	synonymous	Exon 1 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.66G>A	p.Pro22Pro	synonymous	Exon 1 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.66G>A	p.Pro22Pro	synonymous	Exon 1 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes AF: 0.00000929 AC: 1 AN: 107650 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000957

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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 649437 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 194787

African (AFR) AF: 0.00 AC: 0 AN: 12565

American (AMR) AF: 0.00 AC: 0 AN: 1185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4210

East Asian (EAS) AF: 0.00 AC: 0 AN: 3332

South Asian (SAS) AF: 0.00 AC: 0 AN: 12662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1134

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 591109

Other (OTH) AF: 0.00 AC: 0 AN: 21762

GnomAD4 genome AF: 0.00000929 AC: 1 AN: 107650 Hom.: 0 Cov.: 22 AF XY: 0.0000308 AC XY: 1 AN XY: 32420

African (AFR) AF: 0.00 AC: 0 AN: 30393

American (AMR) AF: 0.0000957 AC: 1 AN: 10450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2584

East Asian (EAS) AF: 0.00 AC: 0 AN: 3425

South Asian (SAS) AF: 0.00 AC: 0 AN: 2736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4453

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 231

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51238

Other (OTH) AF: 0.00 AC: 0 AN: 1470

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	9.6
DANN	Uncertain	0.98
PhyloP100		-0.14
PromoterAI		-0.032	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

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: rs1295395837; hg19: chrX-149862069;