8-17305850-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004686.5(MTMR7):c.1259A>G(p.Asn420Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,702 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
MTMR7
NM_004686.5 missense
NM_004686.5 missense
Scores
12
7
Clinical Significance
Conservation
PhyloP100: 5.03
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTMR7 | NM_004686.5 | c.1259A>G | p.Asn420Ser | missense_variant | 11/14 | ENST00000180173.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTMR7 | ENST00000180173.10 | c.1259A>G | p.Asn420Ser | missense_variant | 11/14 | 1 | NM_004686.5 | P1 | |
MTMR7 | ENST00000521857.5 | c.1259A>G | p.Asn420Ser | missense_variant | 11/13 | 5 | |||
MTMR7 | ENST00000519590.5 | n.271A>G | non_coding_transcript_exon_variant | 2/4 | 4 | ||||
MTMR7 | ENST00000519763.1 | n.395A>G | non_coding_transcript_exon_variant | 4/5 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152172Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251230Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135782
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461412Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 727038
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74470
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2022 | The c.1259A>G (p.N420S) alteration is located in exon 11 (coding exon 11) of the MTMR7 gene. This alteration results from a A to G substitution at nucleotide position 1259, causing the asparagine (N) at amino acid position 420 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at