X-150730566-T-A

Variant names:

• chrX-150730566-T-A
• rs782487202
• NM_001306144.3:c.699T>A

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.699T>A​(p.Asn233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,171,060 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000023 (0 hom. 15 hem.)
• Consequence: MTMR1 NM_001306144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27
• 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=0.21450749).
• BS2: High Hemizygotes in GnomAdExome4 at 15 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.699T>A	p.Asn233Lys	missense	Exon 8 of 16	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.726T>A	p.Asn242Lys	missense	Exon 8 of 16	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.675T>A	p.Asn225Lys	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.699T>A	p.Asn233Lys	missense	Exon 8 of 16	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.675T>A	p.Asn225Lys	missense	Exon 7 of 16	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.675T>A	p.Asn225Lys	missense	Exon 7 of 10	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes AF: 0.00000890 AC: 1 AN: 112399 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000364

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000419 AC: 7 AN: 167138 AF XY: 0.0000918

Gnomad AFR exome AF: 0.0000820

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 24 AN: 1058661 Hom.: 0 Cov.: 25 AF XY: 0.0000450 AC XY: 15 AN XY: 333591

African (AFR) AF: 0.0000393 AC: 1 AN: 25467

American (AMR) AF: 0.00 AC: 0 AN: 32779

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18525

East Asian (EAS) AF: 0.00 AC: 0 AN: 29373

South Asian (SAS) AF: 0.000452 AC: 21 AN: 46467

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3977

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 818150

Other (OTH) AF: 0.0000450 AC: 2 AN: 44427

GnomAD4 genome AF: 0.00000890 AC: 1 AN: 112399 Hom.: 0 Cov.: 23 AF XY: 0.0000289 AC XY: 1 AN XY: 34553

African (AFR) AF: 0.00 AC: 0 AN: 30944

American (AMR) AF: 0.00 AC: 0 AN: 10592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3622

South Asian (SAS) AF: 0.000364 AC: 1 AN: 2751

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6107

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53302

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000824 AC: 10

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.3
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.26
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.093	T
Polyphen		0.22	B
Vest4		0.22
MutPred		0.55		Gain of methylation at N233 (P = 0.0157)
MVP		0.93
ClinPred		0.16	T
GERP RS		-0.24
Varity_R		0.76
gMVP		0.57
Mutation Taster		=90/10	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: rs782487202; hg19: chrX-149899038;