chr8-17306416-G-C

Variant names:

• chr8-17306416-G-C
• rs10503592
• NM_004686.5:c.1152-459C>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.1152-459C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 151,844 control chromosomes in the GnomAD database, including 1,175 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 0.11 (1175 hom., cov: 32)
• Consequence: MTMR7 NM_004686.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR7	NM_004686.5	c.1152-459C>G		intron_variant	Intron 10 of 13	ENST00000180173.10	NP_004677.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR7	ENST00000180173.10	c.1152-459C>G		intron_variant	Intron 10 of 13	1	NM_004686.5	ENSP00000180173.4
MTMR7	ENST00000521857.5	c.1152-459C>G		intron_variant	Intron 10 of 12	5		ENSP00000429733.1
MTMR7	ENST00000519590.5	n.164-459C>G		intron_variant	Intron 1 of 3	4
MTMR7	ENST00000519763.1	n.288-459C>G		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17043 AN: 151724 Hom.: 1175 Cov.: 32

Gnomad AFR AF: 0.0514

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0714

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00368

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.0928

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

GnomAD4 genome AF: 0.112 AC: 17047 AN: 151844 Hom.: 1175 Cov.: 32 AF XY: 0.112 AC XY: 8298 AN XY: 74188

African (AFR) AF: 0.0515 AC: 2136 AN: 41478

American (AMR) AF: 0.0713 AC: 1087 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3468

East Asian (EAS) AF: 0.00369 AC: 19 AN: 5150

South Asian (SAS) AF: 0.0839 AC: 403 AN: 4804

European-Finnish (FIN) AF: 0.191 AC: 2004 AN: 10484

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10660 AN: 67914

Other (OTH) AF: 0.0913 AC: 192 AN: 2102

Alfa AF: 0.143 Hom.: 205

Bravo AF: 0.101

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.69
DANN	Benign	0.45
PhyloP100		-0.19
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: rs10503592; hg19: chr8-17163925;