3-9657375-G-C

Variant names:

• chr3-9657375-G-C
• rs3868891
• NM_001077525.3:c.308+3606G>C

Variant summary

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

The NM_001077525.3(MTMR14):​c.308+3606G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,084 control chromosomes in the GnomAD database, including 4,977 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 0.19 (4977 hom., cov: 32)
• Consequence: MTMR14 NM_001077525.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR14	NM_001077525.3	MANE Select	c.308+3606G>C		intron	N/A	NP_001070993.1
	MTMR14	NM_001400518.1		c.377+3606G>C		intron	N/A	NP_001387447.1
	MTMR14	NM_001400519.1		c.308+3606G>C		intron	N/A	NP_001387448.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR14	ENST00000296003.9	TSL:1 MANE Select	c.308+3606G>C		intron	N/A	ENSP00000296003.5
	MTMR14	ENST00000353332.9	TSL:1	c.308+3606G>C		intron	N/A	ENSP00000323462.8
	MTMR14	ENST00000351233.9	TSL:1	c.308+3606G>C		intron	N/A	ENSP00000334070.7

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29538 AN: 151966 Hom.: 4947 Cov.: 32

Gnomad AFR AF: 0.460

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0603

Gnomad SAS AF: 0.0727

Gnomad FIN AF: 0.0653

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0865

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.195 AC: 29614 AN: 152084 Hom.: 4977 Cov.: 32 AF XY: 0.192 AC XY: 14274 AN XY: 74332

African (AFR) AF: 0.460 AC: 19070 AN: 41422

American (AMR) AF: 0.165 AC: 2522 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3472

East Asian (EAS) AF: 0.0600 AC: 311 AN: 5180

South Asian (SAS) AF: 0.0736 AC: 354 AN: 4812

European-Finnish (FIN) AF: 0.0653 AC: 693 AN: 10608

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0865 AC: 5881 AN: 68012

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.0418 Hom.: 41

Bravo AF: 0.216

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.73
PhyloP100		0.010
Mutation Taster		=100/0	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: rs3868891; hg19: chr3-9699059;