rs774894520

Variant names:

• chr17-58495011-C-A
• rs774894520
• NM_001378067.1:c.3173G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-58495011-C-A
• chr17-58495011-C-T

Variant summary

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

The NM_001378067.1(MTMR4):​c.3173G>T​(p.Arg1058Leu) variant causes a missense change. 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. R1058H) 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: 3.63
• Publications: 3 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]

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, 0.775

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.3173G>T	p.Arg1058Leu	missense	Exon 15 of 18	NP_001364996.1	A0A804HJV7
	MTMR4	NM_001378066.1		c.3143G>T	p.Arg1048Leu	missense	Exon 17 of 20	NP_001364995.1
	MTMR4	NM_004687.5		c.3131G>T	p.Arg1044Leu	missense	Exon 16 of 19	NP_004678.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR4	ENST00000682306.1	MANE Select	c.3173G>T	p.Arg1058Leu	missense	Exon 15 of 18	ENSP00000507664.1	A0A804HJV7
	MTMR4	ENST00000323456.9	TSL:1	c.3131G>T	p.Arg1044Leu	missense	Exon 16 of 19	ENSP00000325285.5	Q9NYA4
	MTMR4	ENST00000955804.1		c.3269G>T	p.Arg1090Leu	missense	Exon 16 of 19	ENSP00000625863.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.52
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.060	T
Polyphen		0.99	D
Vest4		0.66
MutPred		0.37		Loss of MoRF binding (P = 0.0069)
MVP		0.43
MPC		0.86
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.18
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

Other links and lift over

dbSNP: rs774894520; hg19: chr17-56572372; COSMIC: COSV60202722; COSMIC: COSV60202722;