2-64551527-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_203437.4(AFTPH):ā€‹c.53A>Gā€‹(p.Asn18Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000235 in 1,614,036 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

AFTPH
NM_203437.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69
Variant links:
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]

Genome browser will be placed here

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=0.14790615).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AFTPHNM_203437.4 linkuse as main transcriptc.53A>G p.Asn18Ser missense_variant 2/10 ENST00000409933.6 NP_982261.2
LOC105374773XR_007086343.1 linkuse as main transcriptn.5406-263T>C intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AFTPHENST00000409933.6 linkuse as main transcriptc.53A>G p.Asn18Ser missense_variant 2/101 NM_203437.4 ENSP00000387071 A1Q6ULP2-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
250714
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135764
show subpopulations
Gnomad AFR exome
AF:
0.000126
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461784
Hom.:
0
Cov.:
32
AF XY:
0.0000234
AC XY:
17
AN XY:
727196
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000359
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsApr 20, 2024The c.53A>G (p.N18S) alteration is located in exon 2 (coding exon 1) of the AFTPH gene. This alteration results from a A to G substitution at nucleotide position 53, causing the asparagine (N) at amino acid position 18 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0055
T;.;T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D;D;.
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L;L;L
MutationTaster
Benign
0.88
D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.9
N;N;N
REVEL
Benign
0.083
Sift
Benign
0.13
T;T;T
Sift4G
Benign
0.28
T;T;T
Polyphen
0.99
D;.;D
Vest4
0.44
MVP
0.31
MPC
0.38
ClinPred
0.18
T
GERP RS
5.6
Varity_R
0.13
gMVP
0.037

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs184801562; hg19: chr2-64778661; API