rs2302189

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-58506844-A-C
• chr17-58506844-A-G
• chr17-58506844-A-T

Variant summary

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

The NM_001378067.1(MTMR4):​c.932T>G​(p.Val311Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,611,908 control chromosomes in the GnomAD database, including 122,014 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10265 hom., cov: 32)
  • Exomes 𝑓: 0.39 (111749 hom.)
• Consequence: MTMR4 NM_001378067.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 59 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=5.507469E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR4	NM_001378067.1	c.932T>G	p.Val311Gly	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>G	p.Val311Gly	missense_variant	Exon 9 of 18		NM_001378067.1	ENSP00000507664.1
MTMR4	ENST00000323456.9	c.890T>G	p.Val297Gly	missense_variant	Exon 10 of 19	1		ENSP00000325285.5
MTMR4	ENST00000579925.5	c.890T>G	p.Val297Gly	missense_variant	Exon 10 of 18	5		ENSP00000464067.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54649 AN: 151762 Hom.: 10253 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.372

GnomAD2 exomes AF: 0.418 AC: 103741 AN: 248086 AF XY: 0.412

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.618

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.528

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.377

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.387 AC: 564844 AN: 1460028 Hom.: 111749 Cov.: 47 AF XY: 0.386 AC XY: 280422 AN XY: 726242

African (AFR) AF: 0.270 AC: 9052 AN: 33468

American (AMR) AF: 0.598 AC: 26634 AN: 44520

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 10238 AN: 26118

East Asian (EAS) AF: 0.530 AC: 21034 AN: 39668

South Asian (SAS) AF: 0.414 AC: 35647 AN: 86148

European-Finnish (FIN) AF: 0.345 AC: 18151 AN: 52600

Middle Eastern (MID) AF: 0.334 AC: 1926 AN: 5758

European-Non Finnish (NFE) AF: 0.377 AC: 418934 AN: 1111402

Other (OTH) AF: 0.385 AC: 23228 AN: 60346

GnomAD4 genome AF: 0.360 AC: 54678 AN: 151880 Hom.: 10265 Cov.: 32 AF XY: 0.361 AC XY: 26801 AN XY: 74222

African (AFR) AF: 0.275 AC: 11403 AN: 41402

American (AMR) AF: 0.466 AC: 7114 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2700 AN: 5146

South Asian (SAS) AF: 0.408 AC: 1968 AN: 4828

European-Finnish (FIN) AF: 0.346 AC: 3644 AN: 10540

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.372 AC: 25251 AN: 67916

Other (OTH) AF: 0.369 AC: 778 AN: 2108

Alfa AF: 0.378 Hom.: 37508

Bravo AF: 0.375

TwinsUK AF: 0.373 AC: 1382

ALSPAC AF: 0.391 AC: 1506

ESP6500AA AF: 0.279 AC: 1228

ESP6500EA AF: 0.376 AC: 3236

ExAC AF: 0.410 AC: 49772

Asia WGS AF: 0.446 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.68	D;D
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.47	T;T
MetaRNN	Benign	0.00055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	.;L
PhyloP100		3.2
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	.;D
REVEL	Uncertain	0.55
Sift	Benign	0.28	.;T
Sift4G	Benign	0.35	T;T
Polyphen		0.89	.;P
Vest4		0.14
MPC		1.2
ClinPred		0.037	T
GERP RS		4.5
Varity_R		0.34
gMVP		0.70
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2302189; hg19: chr17-56584205; COSMIC: COSV60199588; COSMIC: COSV60199588;