17-58506844-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001378067.1(MTMR4):​c.932T>C​(p.Val311Ala) 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. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20924369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR4	NM_001378067.1	c.932T>C	p.Val311Ala	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>C	p.Val311Ala	missense_variant	Exon 9 of 18		NM_001378067.1	ENSP00000507664.1
MTMR4	ENST00000323456.9	c.890T>C	p.Val297Ala	missense_variant	Exon 10 of 19	1		ENSP00000325285.5
MTMR4	ENST00000579925.5	c.890T>C	p.Val297Ala	missense_variant	Exon 10 of 18	5		ENSP00000464067.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248086 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

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: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

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	0.091
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Benign	0.70
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.64	.;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.63	.;N
REVEL	Benign	0.24
Sift	Benign	0.88	.;T
Sift4G	Benign	0.56	T;T
Polyphen		0.044	.;B
Vest4		0.11
MutPred		0.30		Gain of disorder (P = 0.0293);Gain of disorder (P = 0.0293);
MVP		0.22
MPC		0.79
ClinPred		0.24	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.074
gMVP		0.54

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;