13-25249479-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004685.5(MTMR6):​c.1619G>T​(p.Arg540Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,612 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0315789).

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>T	p.Arg540Leu	missense	Exon 14 of 14	NP_004676.3
	MTMR6	NM_001385230.1		c.1733G>T	p.Arg578Leu	missense	Exon 15 of 15	NP_001372159.1	A0A9L9PXJ0
	MTMR6	NM_001385231.1		c.1565G>T	p.Arg522Leu	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>T	p.Arg540Leu	missense	Exon 14 of 14	ENSP00000371221.5	Q9Y217-1
	MTMR6	ENST00000482345.2	TSL:5	c.1733G>T	p.Arg578Leu	missense	Exon 15 of 15	ENSP00000516657.1	A0A9L9PXJ0
	MTMR6	ENST00000956555.1		c.1631G>T	p.Arg544Leu	missense	Exon 15 of 15	ENSP00000626614.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459612 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725744

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26094

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 86130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110404

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	3.8
DANN	Benign	0.70
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	-0.14	N
PhyloP100		-1.1
PrimateAI	Benign	0.21	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.23
Sift	Benign	0.81	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.38		Loss of MoRF binding (P = 0.0341)
MVP		0.62
MPC		0.15
ClinPred		0.058	T
GERP RS		-5.0
Varity_R		0.062
gMVP		0.30
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV67808542;