chr8-17306416-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.191
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE Protein UniProt
MTMR7NM_004686.5 linkuse as main transcriptc.1152-459C>G intron_variant ENST00000180173.10 NP_004677.3 Q9Y216-1B7Z9Q7B7ZAG8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MTMR7ENST00000180173.10 linkuse as main transcriptc.1152-459C>G intron_variant 1 NM_004686.5 ENSP00000180173.4 Q9Y216-1
MTMR7ENST00000521857.5 linkuse as main transcriptc.1152-459C>G intron_variant 5 ENSP00000429733.1 Q9Y216-2
MTMR7ENST00000519590.5 linkuse as main transcriptn.164-459C>G intron_variant 4
MTMR7ENST00000519763.1 linkuse as main transcriptn.288-459C>G intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.112
AC:
17043
AN:
151724
Hom.:
1175
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.0515
Gnomad4 AMR
AF:
0.0713
Gnomad4 ASJ
AF:
0.138
Gnomad4 EAS
AF:
0.00369
Gnomad4 SAS
AF:
0.0839
Gnomad4 FIN
AF:
0.191
Gnomad4 NFE
AF:
0.157
Gnomad4 OTH
AF:
0.0913
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10503592; hg19: chr8-17163925; API