chr8-17355620-T-C

Variant names:

• chr8-17355620-T-C
• rs9325808
• NM_004686.5:c.468+5497A>G

Variant summary

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

The NM_004686.5(MTMR7):​c.468+5497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,596 control chromosomes in the GnomAD database, including 7,543 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 0.29 (7543 hom., cov: 32)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.814
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR7	NM_004686.5	MANE Select	c.468+5497A>G		intron	N/A	NP_004677.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR7	ENST00000180173.10	TSL:1 MANE Select	c.468+5497A>G		intron	N/A	ENSP00000180173.4
	MTMR7	ENST00000521857.5	TSL:5	c.468+5497A>G		intron	N/A	ENSP00000429733.1
	MTMR7	ENST00000517317.5	TSL:5	n.311-6539A>G		intron	N/A	ENSP00000431000.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44185 AN: 151482 Hom.: 7513 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.292 AC: 44265 AN: 151596 Hom.: 7543 Cov.: 32 AF XY: 0.299 AC XY: 22125 AN XY: 74088

African (AFR) AF: 0.370 AC: 15307 AN: 41386

American (AMR) AF: 0.329 AC: 5013 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 495 AN: 3468

East Asian (EAS) AF: 0.711 AC: 3682 AN: 5176

South Asian (SAS) AF: 0.301 AC: 1447 AN: 4802

European-Finnish (FIN) AF: 0.326 AC: 3384 AN: 10394

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14226 AN: 67814

Other (OTH) AF: 0.275 AC: 579 AN: 2106

Alfa AF: 0.210 Hom.: 2098

Bravo AF: 0.297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.66
PhyloP100		-0.81
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: rs9325808; hg19: chr8-17213129;