7-38463004-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001635.4(AMPH):c.859G>A(p.Ala287Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000288 in 1,596,438 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000028 ( 0 hom. )
Consequence
AMPH
NM_001635.4 missense
NM_001635.4 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 5.96
Genes affected
AMPH (HGNC:471): (amphiphysin) This gene encodes a protein associated with the cytoplasmic surface of synaptic vesicles. A subset of patients with stiff-man syndrome who were also affected by breast cancer are positive for autoantibodies against this protein. Alternate splicing of this gene results in two transcript variants encoding different isoforms. Additional splice variants have been described, but their full length sequences have not been determined. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36633885).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMPH | NM_001635.4 | c.859G>A | p.Ala287Thr | missense_variant | 10/21 | ENST00000356264.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMPH | ENST00000356264.7 | c.859G>A | p.Ala287Thr | missense_variant | 10/21 | 1 | NM_001635.4 | P3 | |
AMPH | ENST00000325590.9 | c.859G>A | p.Ala287Thr | missense_variant | 10/20 | 1 | A2 | ||
AMPH | ENST00000441628.5 | c.112G>A | p.Ala38Thr | missense_variant | 1/12 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152124Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000293 AC: 7AN: 238914Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128332
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GnomAD4 exome AF: 0.0000284 AC: 41AN: 1444314Hom.: 0 Cov.: 30 AF XY: 0.0000223 AC XY: 16AN XY: 716602
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74318
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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 | Dec 28, 2023 | The c.859G>A (p.A287T) alteration is located in exon 10 (coding exon 10) of the AMPH gene. This alteration results from a G to A substitution at nucleotide position 859, causing the alanine (A) at amino acid position 287 to be replaced by a threonine (T). 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
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
0.59
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