rs763915529

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004686.5(MTMR7):​c.1895G>T​(p.Cys632Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C632S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MTMR7
NM_004686.5 missense

Scores

7
7
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.18
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.749

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTMR7NM_004686.5 linkc.1895G>T p.Cys632Phe missense_variant Exon 14 of 14 ENST00000180173.10 NP_004677.3 Q9Y216-1B7Z9Q7B7ZAG8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTMR7ENST00000180173.10 linkc.1895G>T p.Cys632Phe missense_variant Exon 14 of 14 1 NM_004686.5 ENSP00000180173.4 Q9Y216-1
VPS37AENST00000520997.1 linkn.295C>A non_coding_transcript_exon_variant Exon 3 of 3 3
VPS37AENST00000521162.5 linkn.637C>A non_coding_transcript_exon_variant Exon 3 of 3 2
VPS37AENST00000519515.1 linkn.52+1792C>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Pathogenic
0.46
D
BayesDel_noAF
Pathogenic
0.43
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.75
D
MetaSVM
Pathogenic
0.82
D
MutationAssessor
Benign
0.97
L
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-2.9
D
REVEL
Uncertain
0.58
Sift
Uncertain
0.0080
D
Sift4G
Benign
0.35
T
Polyphen
1.0
D
Vest4
0.74
MutPred
0.11
Gain of catalytic residue at C632 (P = 0.0558);
MVP
1.0
MPC
0.17
ClinPred
0.97
D
GERP RS
5.6
Varity_R
0.55
gMVP
0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17157459; API