chrX-150730573-A-G

Variant names:

• chrX-150730573-A-G
• rs371653998
• NM_001306144.3:c.706A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001306144.3(MTMR1):​c.706A>G​(p.Lys236Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. K236Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000051 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.25
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.011281818).

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.706A>G	p.Lys236Glu	missense	Exon 8 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.733A>G	p.Lys245Glu	missense	Exon 8 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.682A>G	p.Lys228Glu	missense	Exon 7 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.706A>G	p.Lys236Glu	missense	Exon 8 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.682A>G	p.Lys228Glu	missense	Exon 7 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.682A>G	p.Lys228Glu	missense	Exon 7 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.000623 AC: 103 AN: 165236 AF XY: 0.00

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.000171

Gnomad ASJ exome AF: 0.000293

Gnomad EAS exome AF: 0.00228

Gnomad FIN exome AF: 0.00123

Gnomad NFE exome AF: 0.000500

Gnomad OTH exome AF: 0.000763

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000512 AC: 54 AN: 1054258 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 329140

⚠️ 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: 25387

American (AMR) AF: 0.00 AC: 0 AN: 32781

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18522

East Asian (EAS) AF: 0.00 AC: 0 AN: 29417

South Asian (SAS) AF: 0.00 AC: 0 AN: 46650

European-Finnish (FIN) AF: 0.00115 AC: 45 AN: 39024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3957

European-Non Finnish (NFE) AF: 0.00000860 AC: 7 AN: 814312

Other (OTH) AF: 0.0000452 AC: 2 AN: 44208

⚠️ 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 Cov.: 23

ExAC AF: 0.00309 AC: 375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	0.31	D
MutationAssessor	Benign	1.2	L
PhyloP100		9.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.58
Sift	Benign	0.30	T
Sift4G	Benign	0.32	T
Polyphen		0.011	B
Vest4		0.32
MVP		0.99
ClinPred		0.022	T
GERP RS		5.2
Varity_R		0.74
gMVP		0.75
Mutation Taster		=58/42	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: rs371653998; hg19: chrX-149899045;