13-25257312-C-G

Variant names:

• chr13-25257312-C-G
• NM_004685.5:c.979G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004685.5(MTMR6):​c.979G>C​(p.Val327Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTMR6 NM_004685.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.597

Genes affected

MTMR6 (HGNC:7453): (myotubularin related protein 6) Enables phosphatidylinositol-3,5-bisphosphate phosphatase activity and phosphatidylinositol-3-phosphatase activity. Involved in phosphatidylinositol dephosphorylation. Located in cytoplasm and nuclear envelope. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091245145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR6	NM_004685.5	c.979G>C	p.Val327Leu	missense_variant	Exon 9 of 14	ENST00000381801.6	NP_004676.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR6	ENST00000381801.6	c.979G>C	p.Val327Leu	missense_variant	Exon 9 of 14	1	NM_004685.5	ENSP00000371221.5
MTMR6	ENST00000482345.2	c.1093G>C	p.Val365Leu	missense_variant	Exon 10 of 15	5		ENSP00000516657.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.979G>C (p.V327L) alteration is located in exon 9 (coding exon 9) of the MTMR6 gene. This alteration results from a G to C substitution at nucleotide position 979, causing the valine (V) at amino acid position 327 to be replaced by a leucine (L). 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	Benign	0.10
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	9.0
DANN	Benign	0.88
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.41	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.096
Sift	Benign	0.47	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.32		Gain of ubiquitination at K323 (P = 0.115);
MVP		0.67
MPC		0.12
ClinPred		0.025	T
GERP RS		2.7
Varity_R		0.085
gMVP		0.38

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: chr13-25831450;