chr8-17310516-G-A

Variant names:

• chr8-17310516-G-A
• rs2285274
• NM_004686.5:c.1101+995C>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.1101+995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,182 control chromosomes in the GnomAD database, including 1,418 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 0.10 (1418 hom., cov: 32)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

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 (SAS) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR7	NM_004686.5	c.1101+995C>T		intron_variant	Intron 9 of 13	ENST00000180173.10	NP_004677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR7	ENST00000180173.10	c.1101+995C>T		intron_variant	Intron 9 of 13	1	NM_004686.5	ENSP00000180173.4
MTMR7	ENST00000521857.5	c.1101+995C>T		intron_variant	Intron 9 of 12	5		ENSP00000429733.1
MTMR7	ENST00000519590.5	n.163+995C>T		intron_variant	Intron 1 of 3	4
MTMR7	ENST00000519763.1	n.237+995C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15854 AN: 152064 Hom.: 1409 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.104 AC: 15876 AN: 152182 Hom.: 1418 Cov.: 32 AF XY: 0.111 AC XY: 8293 AN XY: 74406

African (AFR) AF: 0.0390 AC: 1619 AN: 41546

American (AMR) AF: 0.102 AC: 1564 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 740 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2030 AN: 5134

South Asian (SAS) AF: 0.407 AC: 1963 AN: 4824

European-Finnish (FIN) AF: 0.0796 AC: 843 AN: 10596

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6777 AN: 68008

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.107 Hom.: 1752

Bravo AF: 0.0965

Asia WGS AF: 0.380 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.091
DANN	Benign	0.33
PhyloP100		-1.6
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: rs2285274; hg19: chr8-17168025;