rs9983

Variant names:

• chr22-30027755-G-A
• rs9983
• NM_021090.4:c.*1954G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021090.4(MTMR3):​c.*1954G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,666 control chromosomes in the GnomAD database, including 1,919 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 0.16 (1915 hom., cov: 33)
  • Exomes 𝑓: 0.14 (4 hom.)
• Consequence: MTMR3 NM_021090.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 28 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021090.4. 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
	MTMR3	NM_021090.4	MANE Select	c.*1954G>A		3_prime_UTR	Exon 20 of 20	NP_066576.1	Q13615-1
	MTMR3	NM_153050.3		c.*1954G>A		3_prime_UTR	Exon 20 of 20	NP_694690.1	Q13615-2
	MTMR3	NM_153051.3		c.*1954G>A		3_prime_UTR	Exon 19 of 19	NP_694691.1	Q13615-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR3	ENST00000401950.7	TSL:1 MANE Select	c.*1954G>A		3_prime_UTR	Exon 20 of 20	ENSP00000384651.3	Q13615-1
	MTMR3	ENST00000908090.1		c.*1954G>A		3_prime_UTR	Exon 21 of 21	ENSP00000578149.1
	MTMR3	ENST00000908091.1		c.*1954G>A		3_prime_UTR	Exon 22 of 22	ENSP00000578150.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23576 AN: 152072 Hom.: 1916 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.141 AC: 67 AN: 476 Hom.: 4 Cov.: 0 AF XY: 0.148 AC XY: 42 AN XY: 284

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.130 AC: 18 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.145 AC: 49 AN: 338

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.155 AC: 23597 AN: 152190 Hom.: 1915 Cov.: 33 AF XY: 0.156 AC XY: 11596 AN XY: 74398

African (AFR) AF: 0.157 AC: 6500 AN: 41490

American (AMR) AF: 0.118 AC: 1802 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 378 AN: 3472

East Asian (EAS) AF: 0.118 AC: 611 AN: 5190

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4820

European-Finnish (FIN) AF: 0.156 AC: 1649 AN: 10582

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11126 AN: 68008

Other (OTH) AF: 0.132 AC: 278 AN: 2114

Alfa AF: 0.153 Hom.: 2373

Bravo AF: 0.150

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs9983; hg19: chr22-30423744;