chr8-11295294-T-A

Position:

• chr8-11295294-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015458.4(MTMR9):​c.283T>A​(p.Ser95Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MTMR9 NM_015458.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.87

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR9	NM_015458.4	c.283T>A	p.Ser95Thr	missense_variant	2/10	ENST00000221086.8
MTMR9	XM_047422125.1	c.283T>A	p.Ser95Thr	missense_variant	2/11
MTMR9	XM_017013753.3	c.283T>A	p.Ser95Thr	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR9	ENST00000221086.8	c.283T>A	p.Ser95Thr	missense_variant	2/10	1	NM_015458.4	P1
MTMR9	ENST00000530200.1	c.283T>A	p.Ser95Thr	missense_variant, NMD_transcript_variant	2/11	1
MTMR9	ENST00000526292.1	c.28T>A	p.Ser10Thr	missense_variant	2/10	2
MTMR9	ENST00000528389.1	n.520T>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 29, 2023

The c.283T>A (p.S95T) alteration is located in exon 2 (coding exon 2) of the MTMR9 gene. This alteration results from a T to A substitution at nucleotide position 283, causing the serine (S) at amino acid position 95 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Uncertain	0.46	D
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.51
Sift	Benign	0.14	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.048	B;.
Vest4		0.76
MutPred		0.60		Gain of catalytic residue at S95 (P = 0.0363);.;
MVP		0.92
MPC		0.013
ClinPred		0.83	D
GERP RS		5.5
Varity_R		0.30
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-11152803;