17-58507147-T-C

Variant names:

• chr17-58507147-T-C
• rs2302190
• NM_001378067.1:c.880A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378067.1(MTMR4):​c.880A>G​(p.Ser294Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,613,758 control chromosomes in the GnomAD database, including 43,031 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.27 (6645 hom., cov: 31)
  • Exomes 𝑓: 0.21 (36386 hom.)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 40 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003486067).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

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.880A>G	p.Ser294Gly	missense	Exon 8 of 18	NP_001364996.1	A0A804HJV7
	MTMR4	NM_001378066.1		c.850A>G	p.Ser284Gly	missense	Exon 10 of 20	NP_001364995.1
	MTMR4	NM_004687.5		c.838A>G	p.Ser280Gly	missense	Exon 9 of 19	NP_004678.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR4	ENST00000682306.1	MANE Select	c.880A>G	p.Ser294Gly	missense	Exon 8 of 18	ENSP00000507664.1	A0A804HJV7
	MTMR4	ENST00000323456.9	TSL:1	c.838A>G	p.Ser280Gly	missense	Exon 9 of 19	ENSP00000325285.5	Q9NYA4
	MTMR4	ENST00000955804.1		c.976A>G	p.Ser326Gly	missense	Exon 9 of 19	ENSP00000625863.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41598 AN: 151888 Hom.: 6618 Cov.: 31

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.256

GnomAD2 exomes AF: 0.240 AC: 60273 AN: 251214 AF XY: 0.244

Gnomad AFR exome AF: 0.431

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.302

Gnomad EAS exome AF: 0.327

Gnomad FIN exome AF: 0.224

Gnomad NFE exome AF: 0.201

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.214 AC: 312807 AN: 1461750 Hom.: 36386 Cov.: 34 AF XY: 0.219 AC XY: 159332 AN XY: 727210

African (AFR) AF: 0.443 AC: 14815 AN: 33470

American (AMR) AF: 0.137 AC: 6126 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 7910 AN: 26134

East Asian (EAS) AF: 0.305 AC: 12118 AN: 39698

South Asian (SAS) AF: 0.348 AC: 30057 AN: 86252

European-Finnish (FIN) AF: 0.215 AC: 11493 AN: 53414

Middle Eastern (MID) AF: 0.341 AC: 1968 AN: 5764

European-Non Finnish (NFE) AF: 0.192 AC: 213520 AN: 1111904

Other (OTH) AF: 0.245 AC: 14800 AN: 60392

GnomAD4 genome AF: 0.274 AC: 41671 AN: 152008 Hom.: 6645 Cov.: 31 AF XY: 0.274 AC XY: 20392 AN XY: 74306

African (AFR) AF: 0.429 AC: 17791 AN: 41426

American (AMR) AF: 0.181 AC: 2760 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3470

East Asian (EAS) AF: 0.329 AC: 1693 AN: 5152

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4816

European-Finnish (FIN) AF: 0.219 AC: 2317 AN: 10568

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13561 AN: 67980

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.227 Hom.: 14271

Bravo AF: 0.275

TwinsUK AF: 0.196 AC: 728

ALSPAC AF: 0.189 AC: 729

ESP6500AA AF: 0.418 AC: 1840

ESP6500EA AF: 0.203 AC: 1750

ExAC AF: 0.246 AC: 29851

Asia WGS AF: 0.356 AC: 1235 AN: 3478

EpiCase AF: 0.210

EpiControl AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.66	N
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.28
Sift	Benign	0.52	T
Sift4G	Benign	0.39	T
Polyphen		0.0	B
Vest4		0.051
MPC		0.59
ClinPred		0.0041	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.090
gMVP		0.49
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2302190; hg19: chr17-56584508; COSMIC: COSV60199749; COSMIC: COSV60199749;