chr8-17372243-C-A

Variant names:

• chr8-17372243-C-A
• rs12676388
• NM_004686.5:c.147+875G>T

Variant summary

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

The NM_004686.5(MTMR7):​c.147+875G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,102 control chromosomes in the GnomAD database, including 1,794 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 0.14 (1794 hom., cov: 31)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 2 publications found

Genes affected

MTMR7 (HGNC:7454): (myotubularin related protein 7) This gene encodes a member of the myotubularin family of tyrosine/dual-specificity phosphatases. The encoded protein is characterized by four distinct domains that are conserved among all members of the myotubularin family: the glucosyltransferase, Rab-like GTPase activator and myotubularins domain, the Rac-induced recruitment domain, the protein tyrosine phosphatases and dual-specificity phosphatases domain and the suppressor of variegation 3-9, enhancer-of-zeste, and trithorax interaction domain. This protein dephosphorylates the target substrates phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate. A pseudogene of this gene is found on chromosome 5. [provided by RefSeq, Mar 2009]

LOC102724838 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004686.5. 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
	MTMR7	NM_004686.5	MANE Select	c.147+875G>T		intron	N/A	NP_004677.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR7	ENST00000180173.10	TSL:1 MANE Select	c.147+875G>T		intron	N/A	ENSP00000180173.4	Q9Y216-1
	MTMR7	ENST00000915631.1		c.25-1044G>T		intron	N/A	ENSP00000585690.1
	MTMR7	ENST00000915632.1		c.147+875G>T		intron	N/A	ENSP00000585691.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20896 AN: 151984 Hom.: 1782 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.138 AC: 20945 AN: 152102 Hom.: 1794 Cov.: 31 AF XY: 0.140 AC XY: 10412 AN XY: 74352

African (AFR) AF: 0.108 AC: 4459 AN: 41464

American (AMR) AF: 0.112 AC: 1708 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2008 AN: 5170

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4824

European-Finnish (FIN) AF: 0.143 AC: 1509 AN: 10570

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9460 AN: 67996

Other (OTH) AF: 0.130 AC: 276 AN: 2116

Alfa AF: 0.139 Hom.: 998

Bravo AF: 0.129

Asia WGS AF: 0.315 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		-0.017
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: rs12676388; hg19: chr8-17229752;