rs9983

Positions:

• chr22-30027755-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR3	NM_021090.4	c.*1954G>A		3_prime_UTR_variant	20/20	ENST00000401950.7
HORMAD2-AS1	NR_110541.2	n.362-9026C>T		intron_variant, non_coding_transcript_variant
MTMR3	NM_153050.3	c.*1954G>A		3_prime_UTR_variant	20/20
MTMR3	NM_153051.3	c.*1954G>A		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR3	ENST00000401950.7	c.*1954G>A		3_prime_UTR_variant	20/20	1	NM_021090.4	P4
	ENST00000624945.1	n.482C>T		non_coding_transcript_exon_variant	1/1
HORMAD2-AS1	ENST00000429350.5	n.335-9026C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 EAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.145

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

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.132

Alfa AF: 0.153 Hom.: 1791

Bravo AF: 0.150

Asia WGS AF: 0.173 AC: 600 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9983; hg19: chr22-30423744;