rs5763662

chr22-29982714-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021090.4(MTMR3):c.210+3662C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 152,090 control chromosomes in the GnomAD database, including 369 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.041 (369 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTMR3 NM_021090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR3	NM_021090.4	c.210+3662C>T		intron_variant		ENST00000401950.7
MTMR3	NM_153050.3	c.210+3662C>T		intron_variant
MTMR3	NM_153051.3	c.210+3662C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR3	ENST00000401950.7	c.210+3662C>T		intron_variant		1	NM_021090.4	P4
	ENST00000624945.1	n.45523G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6182 AN: 151972 Hom.: 368 Cov.: 32

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0427

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0407 AC: 6188 AN: 152090 Hom.: 369 Cov.: 32 AF XY: 0.0469 AC XY: 3489 AN XY: 74346

Gnomad4 AFR AF: 0.00979

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0432

Alfa AF: 0.0283 Hom.: 111

Bravo AF: 0.0394

Asia WGS AF: 0.172 AC: 596 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
Dann	Benign	0.49

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: rs5763662; hg19: chr22-30378703;