chr3-50355356-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007024.5(TMEM115):c.1043C>T(p.Pro348Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000722 in 1,495,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
TMEM115
NM_007024.5 missense
NM_007024.5 missense
Scores
2
5
12
Clinical Significance
Conservation
PhyloP100: 5.60
Genes affected
TMEM115 (HGNC:30055): (transmembrane protein 115) Enables identical protein binding activity. Involved in retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum. Located in Golgi cisterna membrane and nucleus. Colocalizes with Golgi transport complex. [provided by Alliance of Genome Resources, Apr 2022]
CYB561D2 (HGNC:30253): (cytochrome b561 family member D2) Enables heme binding activity and transmembrane monodehydroascorbate reductase activity. Involved in ascorbate homeostasis. Predicted to be located in vesicle. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20264864).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM115 | NM_007024.5 | c.1043C>T | p.Pro348Leu | missense_variant | 2/2 | ENST00000266025.4 | |
LOC127898564 | NR_183066.1 | n.276-2762G>A | intron_variant, non_coding_transcript_variant | ||||
CYB561D2 | NR_111912.2 | n.275+3796G>A | intron_variant, non_coding_transcript_variant | ||||
LOC127898564 | NR_183067.1 | n.389+3310G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM115 | ENST00000266025.4 | c.1043C>T | p.Pro348Leu | missense_variant | 2/2 | 1 | NM_007024.5 | P1 | |
CYB561D2 | ENST00000490926.1 | n.365-2762G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000728 AC: 12AN: 164924Hom.: 0 AF XY: 0.0000798 AC XY: 7AN XY: 87752
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GnomAD4 exome AF: 0.0000752 AC: 101AN: 1343576Hom.: 0 Cov.: 30 AF XY: 0.0000773 AC XY: 51AN XY: 659514
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74344
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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 | May 31, 2023 | The c.1043C>T (p.P348L) alteration is located in exon 2 (coding exon 2) of the TMEM115 gene. This alteration results from a C to T substitution at nucleotide position 1043, causing the proline (P) at amino acid position 348 to be replaced by a leucine (L). 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
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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