chr8-17324263-T-G

Variant names:

• chr8-17324263-T-G
• rs7003503
• NM_004686.5:c.865+6887A>C

Variant summary

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

The NM_004686.5(MTMR7):​c.865+6887A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,072 control chromosomes in the GnomAD database, including 8,417 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 0.30 (8417 hom., cov: 32)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 5 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]

VPS37A (HGNC:24928): (VPS37A subunit of ESCRT-I) This gene belongs to the VPS37 family, and encodes a component of the ESCRT-I (endosomal sorting complex required for transport I) protein complex, required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. Expression of this gene is downregulated in hepatocellular carcinoma, and mutations in this gene are associated with autosomal recessive spastic paraplegia-53. A related pseudogene has been identified on chromosome 5. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

VPS37A Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 53

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• complex hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 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.865+6887A>C		intron	N/A	NP_004677.3
	VPS37A	NM_001363173.2		c.*1-6007T>G		intron	N/A	NP_001350102.1	Q8NEZ2-1
	VPS37A	NM_001363172.2		c.*1-6007T>G		intron	N/A	NP_001350101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR7	ENST00000180173.10	TSL:1 MANE Select	c.865+6887A>C		intron	N/A	ENSP00000180173.4	Q9Y216-1
	MTMR7	ENST00000915631.1		c.742+6887A>C		intron	N/A	ENSP00000585690.1
	MTMR7	ENST00000915632.1		c.733-12627A>C		intron	N/A	ENSP00000585691.1

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45259 AN: 151954 Hom.: 8389 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.298 AC: 45335 AN: 152072 Hom.: 8417 Cov.: 32 AF XY: 0.301 AC XY: 22347 AN XY: 74342

African (AFR) AF: 0.516 AC: 21374 AN: 41458

American (AMR) AF: 0.316 AC: 4826 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2176 AN: 5154

South Asian (SAS) AF: 0.146 AC: 706 AN: 4826

European-Finnish (FIN) AF: 0.270 AC: 2859 AN: 10584

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12177 AN: 67988

Other (OTH) AF: 0.267 AC: 565 AN: 2116

Alfa AF: 0.219 Hom.: 12429

Bravo AF: 0.317

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.39
PhyloP100		-0.27
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: rs7003503; hg19: chr8-17181772;