rs17646919

Positions:

• chr22-30004872-A-G

Variant summary

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

The NM_021090.4(MTMR3):​c.671+1879A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0532 in 152,362 control chromosomes in the GnomAD database, including 311 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 0.053 (311 hom., cov: 32)
  • Exomes 𝑓: 0.067 (0 hom.)
• Consequence: MTMR3 NM_021090.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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]

ENSG00000279159 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR3	NM_021090.4	c.671+1879A>G		intron_variant		ENST00000401950.7	NP_066576.1
MTMR3	NM_153050.3	c.671+1879A>G		intron_variant			NP_694690.1
MTMR3	NM_153051.3	c.671+1879A>G		intron_variant			NP_694691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR3	ENST00000401950.7	c.671+1879A>G		intron_variant		1	NM_021090.4	ENSP00000384651.3

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8106 AN: 152214 Hom.: 312 Cov.: 32

Gnomad AFR AF: 0.0139

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0728

Gnomad ASJ AF: 0.0718

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0460

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.0736

GnomAD4 exome AF: 0.0667 AC: 2 AN: 30 Hom.: 0 Cov.: 0 AF XY: 0.0556 AC XY: 1 AN XY: 18

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0769

GnomAD4 genome AF: 0.0532 AC: 8101 AN: 152332 Hom.: 311 Cov.: 32 AF XY: 0.0499 AC XY: 3721 AN XY: 74510

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0728

Gnomad4 ASJ AF: 0.0718

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.0460

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0724

Alfa AF: 0.0773 Hom.: 824

Bravo AF: 0.0572

Asia WGS AF: 0.00808 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.68
DANN	Benign	0.67

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: rs17646919; hg19: chr22-30400861;