13-25249479-C-G

Variant names:

• chr13-25249479-C-G
• rs772892485
• NM_004685.5:c.1619G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004685.5(MTMR6):​c.1619G>C​(p.Arg540Pro) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R540C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MTMR6 NM_004685.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.090663046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004685.5. 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
	MTMR6	NM_004685.5	MANE Select	c.1619G>C	p.Arg540Pro	missense	Exon 14 of 14	NP_004676.3
	MTMR6	NM_001385230.1		c.1733G>C	p.Arg578Pro	missense	Exon 15 of 15	NP_001372159.1	A0A9L9PXJ0
	MTMR6	NM_001385231.1		c.1565G>C	p.Arg522Pro	missense	Exon 14 of 14	NP_001372160.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR6	ENST00000381801.6	TSL:1 MANE Select	c.1619G>C	p.Arg540Pro	missense	Exon 14 of 14	ENSP00000371221.5	Q9Y217-1
	MTMR6	ENST00000482345.2	TSL:5	c.1733G>C	p.Arg578Pro	missense	Exon 15 of 15	ENSP00000516657.1	A0A9L9PXJ0
	MTMR6	ENST00000956555.1		c.1631G>C	p.Arg544Pro	missense	Exon 15 of 15	ENSP00000626614.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.091	T
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.21
Sift	Benign	0.21	T
Sift4G	Benign	0.24	T
Polyphen		0.11	B
Vest4		0.20
MutPred		0.38		Loss of MoRF binding (P = 0.0027)
MVP		0.77
MPC		0.21
ClinPred		0.29	T
GERP RS		-5.0
Varity_R		0.28
gMVP		0.53
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs772892485; hg19: chr13-25823617;