2-64552151-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_203437.4(AFTPH):c.677G>A(p.Ser226Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000989 in 1,613,972 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 1 hom. )
Consequence
AFTPH
NM_203437.4 missense
NM_203437.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 5.17
Genes affected
AFTPH (HGNC:25951): (aftiphilin) Enables clathrin binding activity. Predicted to be involved in intracellular transport. Located in Golgi apparatus; cytosol; and nucleoplasm. Part of AP-1 adaptor complex. [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=0.09227151).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AFTPH | NM_203437.4 | c.677G>A | p.Ser226Asn | missense_variant | 2/10 | ENST00000409933.6 | NP_982261.2 | |
LOC105374773 | XR_007086343.1 | n.5406-887C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AFTPH | ENST00000409933.6 | c.677G>A | p.Ser226Asn | missense_variant | 2/10 | 1 | NM_203437.4 | ENSP00000387071 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000565 AC: 86AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000442 AC: 111AN: 251070Hom.: 0 AF XY: 0.000435 AC XY: 59AN XY: 135704
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GnomAD4 exome AF: 0.00103 AC: 1511AN: 1461762Hom.: 1 Cov.: 32 AF XY: 0.00103 AC XY: 747AN XY: 727166
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GnomAD4 genome AF: 0.000565 AC: 86AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41AN XY: 74358
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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 | Aug 12, 2021 | The c.677G>A (p.S226N) alteration is located in exon 2 (coding exon 1) of the AFTPH gene. This alteration results from a G to A substitution at nucleotide position 677, causing the serine (S) at amino acid position 226 to be replaced by an asparagine (N). 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;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
B;.;B
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