rs11250127

chr8-11312700-G-Achr8-11312700-G-C

Variant summary

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

The NM_015458.4(MTMR9):c.972-2223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,106 control chromosomes in the GnomAD database, including 11,263 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 0.36 (11263 hom., cov: 33)
• Consequence: MTMR9 NM_015458.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

Genes affected

MTMR9 (HGNC:14596): (myotubularin related protein 9) This gene encodes a myotubularin-related protein that is atypical to most other members of the myotubularin-related protein family because it has no dual-specificity phosphatase domain. The encoded protein contains a double-helical motif similar to the SET interaction domain, which is thought to have a role in the control of cell proliferation. In mouse, a protein similar to the encoded protein binds with MTMR7, and together they dephosphorylate phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR9	NM_015458.4	c.972-2223G>A		intron_variant		ENST00000221086.8
MTMR9	XM_011543831.3	c.384-2223G>A		intron_variant
MTMR9	XM_017013753.3	c.972-2165G>A		intron_variant
MTMR9	XM_047422125.1	c.972-2223G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR9	ENST00000221086.8	c.972-2223G>A		intron_variant		1	NM_015458.4	P1
MTMR9	ENST00000530200.1	c.*718-2223G>A		intron_variant, NMD_transcript_variant		1
MTMR9	ENST00000526292.1	c.717-2223G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55096 AN: 151988 Hom.: 11262 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.362 AC: 55110 AN: 152106 Hom.: 11263 Cov.: 33 AF XY: 0.370 AC XY: 27510 AN XY: 74344

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.375

Alfa AF: 0.211 Hom.: 500

Bravo AF: 0.349

Asia WGS AF: 0.521 AC: 1812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.8
Dann	Benign	0.56

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: rs11250127; hg19: chr8-11170209;