rs12537

chr22-30027471-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021090.4(MTMR3):c.*1670C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,638 control chromosomes in the GnomAD database, including 12,551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12502 hom., cov: 32)
  • Exomes 𝑓: 0.40 (49 hom.)
• Consequence: MTMR3 NM_021090.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.431

Genes affected

MTMR3 (HGNC:7451): (myotubularin related protein 3) This gene encodes a member of the myotubularin dual specificity protein phosphatase gene family. The encoded protein is structurally similar to myotubularin but in addition contains a FYVE domain and an N-terminal PH-GRAM domain. The protein can self-associate and also form heteromers with another myotubularin related protein. The protein binds to phosphoinositide lipids through the PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The encoded protein has been observed to have a perinuclear, possibly membrane-bound, distribution in cells, but it has also been found free in the cytoplasm. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

(HGNC:):

HORMAD2-AS1 (HGNC:50729): (HORMAD2 and MTMR3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-30027471-C-T is Benign according to our data. Variant chr22-30027471-C-T is described in ClinVar as [Benign]. Clinvar id is 1225402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR3	NM_021090.4	c.*1670C>T		3_prime_UTR_variant	20/20	ENST00000401950.7
HORMAD2-AS1	NR_110541.2	n.362-8742G>A		intron_variant, non_coding_transcript_variant
MTMR3	NM_153050.3	c.*1670C>T		3_prime_UTR_variant	20/20
MTMR3	NM_153051.3	c.*1670C>T		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR3	ENST00000401950.7	c.*1670C>T		3_prime_UTR_variant	20/20	1	NM_021090.4	P4
	ENST00000624945.1	n.766G>A		non_coding_transcript_exon_variant	1/1
HORMAD2-AS1	ENST00000429350.5	n.335-8742G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60933 AN: 151936 Hom.: 12489 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.405

GnomAD4 exome AF: 0.396 AC: 231 AN: 584 Hom.: 49 Cov.: 0 AF XY: 0.368 AC XY: 126 AN XY: 342

Gnomad4 EAS exome AF: 0.420

Gnomad4 FIN exome AF: 0.388

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.401 AC: 60997 AN: 152054 Hom.: 12502 Cov.: 32 AF XY: 0.406 AC XY: 30164 AN XY: 74320

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.366

Gnomad4 OTH AF: 0.402

Alfa AF: 0.373 Hom.: 24306

Bravo AF: 0.401

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 2019

This variant is associated with the following publications: (PMID: 22971574) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.6
Dann	Benign	0.42

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: rs12537; hg19: chr22-30423460; COSMIC: COSV60303822; COSMIC: COSV60303822;