17-58506844-A-T

Variant names:

• chr17-58506844-A-T
• rs2302189
• NM_001378067.1:c.932T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001378067.1(MTMR4):​c.932T>A​(p.Val311Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,258 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR4	NM_001378067.1	c.932T>A	p.Val311Glu	missense_variant	Exon 9 of 18	ENST00000682306.1	NP_001364996.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR4	ENST00000682306.1	c.932T>A	p.Val311Glu	missense_variant	Exon 9 of 18		NM_001378067.1	ENSP00000507664.1
MTMR4	ENST00000323456.9	c.890T>A	p.Val297Glu	missense_variant	Exon 10 of 19	1		ENSP00000325285.5
MTMR4	ENST00000579925.5	c.890T>A	p.Val297Glu	missense_variant	Exon 10 of 18	5		ENSP00000464067.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460258 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 726376

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	22
DANN	Benign	0.93
DEOGEN2	Uncertain	0.57	D;T
Eigen	Benign	-0.091
Eigen_PC	Benign	0.064
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.70	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Uncertain	0.11	D
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	.;N
REVEL	Uncertain	0.41
Sift	Benign	0.30	.;T
Sift4G	Benign	0.30	T;T
Polyphen		0.24	.;B
Vest4		0.39
MutPred		0.40		Gain of solvent accessibility (P = 0.0078);Gain of solvent accessibility (P = 0.0078);
MVP		0.37
MPC		1.7
ClinPred		0.85	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.35
gMVP		0.72

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

LitVar

Other links and lift over

dbSNP: rs2302189; hg19: chr17-56584205;