17-58491758-C-G

Variant names:

• chr17-58491758-C-G
• rs148218230
• NM_001378067.1:c.3535G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001378067.1(MTMR4):​c.3535G>C​(p.Val1179Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. V1179I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

MTMR4 (HGNC:7452): (myotubularin related protein 4) Enables protein phosphatase binding activity. Involved in regulation of phosphatidylinositol dephosphorylation. Located in endosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299242 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.803

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378067.1. 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
	MTMR4	NM_001378067.1	MANE Select	c.3535G>C	p.Val1179Leu	missense	Exon 18 of 18	NP_001364996.1	A0A804HJV7
	MTMR4	NM_001378066.1		c.3505G>C	p.Val1169Leu	missense	Exon 20 of 20	NP_001364995.1
	MTMR4	NM_004687.5		c.3493G>C	p.Val1165Leu	missense	Exon 19 of 19	NP_004678.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR4	ENST00000682306.1	MANE Select	c.3535G>C	p.Val1179Leu	missense	Exon 18 of 18	ENSP00000507664.1	A0A804HJV7
	MTMR4	ENST00000323456.9	TSL:1	c.3493G>C	p.Val1165Leu	missense	Exon 19 of 19	ENSP00000325285.5	Q9NYA4
	MTMR4	ENST00000955804.1		c.3631G>C	p.Val1211Leu	missense	Exon 19 of 19	ENSP00000625863.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.65
Sift	Benign	0.17	T
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.68		Loss of sheet (P = 0.0817)
MVP		0.80
MPC		0.98
ClinPred		0.96	D
GERP RS		6.1
Varity_R		0.25
gMVP		0.83

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

Other links and lift over

dbSNP: rs148218230; hg19: chr17-56569119;