chr2-64552016-T-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_203437.4(AFTPH):āc.542T>Gā(p.Ile181Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000521 in 1,613,816 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00020 ( 0 hom., cov: 32)
Exomes š: 0.00055 ( 2 hom. )
Consequence
AFTPH
NM_203437.4 missense
NM_203437.4 missense
Scores
6
13
Clinical Significance
Conservation
PhyloP100: 2.96
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.12247604).
BS2
High Homozygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AFTPH | NM_203437.4 | c.542T>G | p.Ile181Ser | missense_variant | 2/10 | ENST00000409933.6 | NP_982261.2 | |
LOC105374773 | XR_007086343.1 | n.5406-752A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AFTPH | ENST00000409933.6 | c.542T>G | p.Ile181Ser | missense_variant | 2/10 | 1 | NM_203437.4 | ENSP00000387071 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000204 AC: 31AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000228 AC: 57AN: 250114Hom.: 0 AF XY: 0.000222 AC XY: 30AN XY: 135334
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GnomAD4 exome AF: 0.000553 AC: 809AN: 1461650Hom.: 2 Cov.: 32 AF XY: 0.000546 AC XY: 397AN XY: 727116
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GnomAD4 genome AF: 0.000204 AC: 31AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74336
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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 | Mar 20, 2023 | The c.542T>G (p.I181S) alteration is located in exon 2 (coding exon 1) of the AFTPH gene. This alteration results from a T to G substitution at nucleotide position 542, causing the isoleucine (I) at amino acid position 181 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
Benign
T;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;D;T
Sift4G
Benign
T;T;T
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