17-58495106-A-C

Variant names:

• chr17-58495106-A-C
• NM_001378067.1:c.3078T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001378067.1(MTMR4):​c.3078T>G​(p.Asp1026Glu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.555

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR4	NM_001378067.1	c.3078T>G	p.Asp1026Glu	missense_variant	Exon 15 of 18	ENST00000682306.1	NP_001364996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR4	ENST00000682306.1	c.3078T>G	p.Asp1026Glu	missense_variant	Exon 15 of 18		NM_001378067.1	ENSP00000507664.1
MTMR4	ENST00000323456.9	c.3036T>G	p.Asp1012Glu	missense_variant	Exon 16 of 19	1		ENSP00000325285.5
MTMR4	ENST00000579925.5	c.2865T>G	p.Asp955Glu	missense_variant	Exon 15 of 18	5		ENSP00000464067.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3036T>G (p.D1012E) alteration is located in exon 16 (coding exon 15) of the MTMR4 gene. This alteration results from a T to G substitution at nucleotide position 3036, causing the aspartic acid (D) at amino acid position 1012 to be replaced by a glutamic acid (E). 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	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Pathogenic	0.59	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Pathogenic	0.97	D
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.9	.;D
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.70
MutPred		0.51		.;Loss of relative solvent accessibility (P = 0.107);
MVP		0.77
MPC		0.95
ClinPred		0.97	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.69

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: chr17-56572467;