17-58495156-C-A

Variant names:

• chr17-58495156-C-A
• rs775936038
• NM_001378067.1:c.3028G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378067.1(MTMR4):​c.3028G>T​(p.Val1010Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign 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. V1010I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05460757).

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.3028G>T	p.Val1010Phe	missense	Exon 15 of 18	NP_001364996.1	A0A804HJV7
	MTMR4	NM_001378066.1		c.2998G>T	p.Val1000Phe	missense	Exon 17 of 20	NP_001364995.1
	MTMR4	NM_004687.5		c.2986G>T	p.Val996Phe	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.3028G>T	p.Val1010Phe	missense	Exon 15 of 18	ENSP00000507664.1	A0A804HJV7
	MTMR4	ENST00000323456.9	TSL:1	c.2986G>T	p.Val996Phe	missense	Exon 16 of 19	ENSP00000325285.5	Q9NYA4
	MTMR4	ENST00000955804.1		c.3124G>T	p.Val1042Phe	missense	Exon 16 of 19	ENSP00000625863.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251488 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.065	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	7.8
DANN	Benign	0.44
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.24
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.28
Sift	Benign	0.69	T
Sift4G	Benign	0.12	T
Polyphen		0.24	B
Vest4		0.33
MutPred		0.13		Gain of catalytic residue at V996 (P = 0.0719)
MVP		0.20
MPC		0.51
ClinPred		0.042	T
GERP RS		2.0
Varity_R		0.026
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs775936038; hg19: chr17-56572517;