X-150727547-G-A

Position:

• chrX-150727547-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000445323.7(MTMR1):​c.448-137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 405,492 control chromosomes in the GnomAD database, including 35,473 homozygotes. There are 64,974 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (16248 hom., 20061 hem., cov: 23)
  • Exomes 𝑓: 0.50 (35473 hom. 64974 hem.)
  • Failed GnomAD Quality Control
• Consequence: MTMR1 ENST00000445323.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant X-150727547-G-A is Benign according to our data. Variant chrX-150727547-G-A is described in ClinVar as [Benign]. Clinvar id is 1279285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR1	NM_001306144.3	c.448-137G>A		intron_variant		ENST00000445323.7	NP_001293073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR1	ENST00000445323.7	c.448-137G>A		intron_variant		1	NM_001306144.3	ENSP00000414178	A2

Frequencies

GnomAD3 genomes AF: 0.608 AC: 67547 AN: 111051 Hom.: 16252 Cov.: 23 AF XY: 0.602 AC XY: 20003 AN XY: 33243

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.739

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.497 AC: 201521 AN: 405492 Hom.: 35473 AF XY: 0.523 AC XY: 64974 AN XY: 124224

Gnomad4 AFR exome AF: 0.921

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.274

Gnomad4 SAS exome AF: 0.748

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.463

Gnomad4 OTH exome AF: 0.539

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.608 AC: 67599 AN: 111104 Hom.: 16248 Cov.: 23 AF XY: 0.602 AC XY: 20061 AN XY: 33306

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.632

Alfa AF: 0.526 Hom.: 13463

Bravo AF: 0.637

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.020
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs3747313; hg19: chrX-149896019; COSMIC: COSV64900359;