22-29941597-T-C

Position:

• chr22-29941597-T-C

Variant summary

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

The NM_021090.4(MTMR3):​c.-137-15439T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.783 in 151,990 control chromosomes in the GnomAD database, including 47,028 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 0.78 (47028 hom., cov: 32)
• Consequence: MTMR3 NM_021090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR3	NM_021090.4	c.-137-15439T>C		intron_variant		ENST00000401950.7
MTMR3	NM_153050.3	c.-137-15439T>C		intron_variant
MTMR3	NM_153051.3	c.-137-15439T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR3	ENST00000401950.7	c.-137-15439T>C		intron_variant		1	NM_021090.4	P4

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118859 AN: 151872 Hom.: 46974 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.746

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.783 AC: 118977 AN: 151990 Hom.: 47028 Cov.: 32 AF XY: 0.780 AC XY: 57940 AN XY: 74264

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.917

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.749

Alfa AF: 0.747 Hom.: 54651

Bravo AF: 0.789

Asia WGS AF: 0.874 AC: 3040 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.9
DANN	Benign	0.72

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: rs36600; hg19: chr22-30337586;