rs222346

Variant names:

• chrX-150693741-A-C
• rs222346
• NM_001306144.3:c.146+65A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001306144.3(MTMR1):​c.146+65A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 614,465 control chromosomes in the GnomAD database, including 220,242 homozygotes. There are 173,813 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 1.0 (37807 hom., 28091 hem., cov: 19)
  • Exomes 𝑓: 1.0 (220242 hom. 173813 hem.)
  • Failed GnomAD Quality Control
• Consequence: MTMR1 NM_001306144.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.482
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-150693741-A-C is Benign according to our data. Variant chrX-150693741-A-C is described in ClinVar as Benign. ClinVar VariationId is 1257576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.998 is higher than 0.05.

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.146+65A>C		intron	N/A	NP_001293073.1	F8WA39
	MTMR1	NM_001353990.2		c.146+65A>C		intron	N/A	NP_001340919.1	E9PPP8
	MTMR1	NM_003828.5		c.146+65A>C		intron	N/A	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.146+65A>C		intron	N/A	ENSP00000414178.2	F8WA39
	MTMR1	ENST00000370390.7	TSL:1	c.146+65A>C		intron	N/A	ENSP00000359417.3	Q13613-1
	MTMR1	ENST00000542156.5	TSL:1	c.146+65A>C		intron	N/A	ENSP00000445281.1	Q8NEC6

Frequencies

GnomAD3 genomes AF: 1.00 AC: 103686 AN: 103689 Hom.: 37815 Cov.: 19

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome AF: 1.00 AC: 614381 AN: 614465 Hom.: 220242 AF XY: 1.00 AC XY: 173813 AN XY: 173813

African (AFR) AF: 1.00 AC: 11941 AN: 11941

American (AMR) AF: 1.00 AC: 822 AN: 822

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3836 AN: 3836

East Asian (EAS) AF: 0.999 AC: 2922 AN: 2924

South Asian (SAS) AF: 1.00 AC: 11555 AN: 11555

European-Finnish (FIN) AF: 1.00 AC: 337 AN: 337

Middle Eastern (MID) AF: 0.999 AC: 1052 AN: 1053

European-Non Finnish (NFE) AF: 1.00 AC: 561551 AN: 561630

Other (OTH) AF: 1.00 AC: 20365 AN: 20367

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 103708 AN: 103711 Hom.: 37807 Cov.: 19 AF XY: 1.00 AC XY: 28091 AN XY: 28091

African (AFR) AF: 1.00 AC: 29054 AN: 29054

American (AMR) AF: 1.00 AC: 10155 AN: 10155

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2549 AN: 2549

East Asian (EAS) AF: 1.00 AC: 3135 AN: 3136

South Asian (SAS) AF: 1.00 AC: 2344 AN: 2344

European-Finnish (FIN) AF: 1.00 AC: 3911 AN: 3911

Middle Eastern (MID) AF: 1.00 AC: 208 AN: 208

European-Non Finnish (NFE) AF: 1.00 AC: 50293 AN: 50295

Other (OTH) AF: 1.00 AC: 1435 AN: 1435

Alfa AF: 1.00 Hom.: 8136

Bravo AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.41
PhyloP100		-0.48
PromoterAI		0.048	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs222346; hg19: chrX-149862214;