rs201904466

Variant names:

• chr3-9672734-A-G
• rs201904466
• NM_001077525.3:c.727A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001077525.3(MTMR14):​c.727A>G​(p.Thr243Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00054 (0 hom.)
• Consequence: MTMR14 NM_001077525.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:5
• Conservation: PhyloP100: 8.58
• Publications: 6 publications found

Genes affected

MTMR14 (HGNC:26190): (myotubularin related protein 14) This gene encodes a myotubularin-related protein. The encoded protein is a phosphoinositide phosphatase that specifically dephosphorylates phosphatidylinositol 3,5-biphosphate and phosphatidylinositol 3-phosphate. Mutations in this gene are correlated with autosomal dominant centronuclear myopathy. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 18.[provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4128163).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077525.3. 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
	MTMR14	NM_001077525.3	MANE Select	c.727A>G	p.Thr243Ala	missense	Exon 7 of 19	NP_001070993.1	Q8NCE2-1
	MTMR14	NM_001400518.1		c.796A>G	p.Thr266Ala	missense	Exon 8 of 20	NP_001387447.1
	MTMR14	NM_001400519.1		c.724A>G	p.Thr242Ala	missense	Exon 7 of 19	NP_001387448.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR14	ENST00000296003.9	TSL:1 MANE Select	c.727A>G	p.Thr243Ala	missense	Exon 7 of 19	ENSP00000296003.5	Q8NCE2-1
	MTMR14	ENST00000353332.9	TSL:1	c.727A>G	p.Thr243Ala	missense	Exon 7 of 18	ENSP00000323462.8	Q8NCE2-2
	MTMR14	ENST00000351233.9	TSL:1	c.727A>G	p.Thr243Ala	missense	Exon 7 of 17	ENSP00000334070.7	Q8NCE2-3

Frequencies

GnomAD3 genomes AF: 0.000375 AC: 57 AN: 151904 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000244 AC: 61 AN: 249570 AF XY: 0.000229

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000503

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000540 AC: 789 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.000527 AC XY: 383 AN XY: 727244

African (AFR) AF: 0.000119 AC: 4 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

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

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53420

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

European-Non Finnish (NFE) AF: 0.000689 AC: 766 AN: 1112004

Other (OTH) AF: 0.000248 AC: 15 AN: 60396

GnomAD4 genome AF: 0.000375 AC: 57 AN: 151904 Hom.: 0 Cov.: 32 AF XY: 0.000297 AC XY: 22 AN XY: 74166

African (AFR) AF: 0.000121 AC: 5 AN: 41322

American (AMR) AF: 0.0000657 AC: 1 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000430 Hom.: 0

Bravo AF: 0.000340

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000240 AC: 2

ExAC AF: 0.000207 AC: 25

EpiCase AF: 0.000382

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	4	-	not provided (4)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.75	D
MutationAssessor	Benign	1.7	L
PhyloP100		8.6
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.0	N
REVEL	Pathogenic	0.73
Sift	Benign	0.042	D
Sift4G	Benign	0.14	T
Polyphen		0.92	P
Vest4		0.79
MVP		0.94
MPC		0.77
ClinPred		0.11	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.74
Mutation Taster		=37/63	disease causing

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: rs201904466; hg19: chr3-9714418; COSMIC: COSV56005537; COSMIC: COSV56005537;