chr2-64551746-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.272A>Gā€‹(p.Asp91Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

AFTPH
NM_203437.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47
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=0.10443041).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AFTPHNM_203437.4 linkuse as main transcriptc.272A>G p.Asp91Gly missense_variant 2/10 ENST00000409933.6 NP_982261.2
LOC105374773XR_007086343.1 linkuse as main transcriptn.5406-482T>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.272A>G p.Asp91Gly missense_variant 2/101 NM_203437.4 ENSP00000387071 A1Q6ULP2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251316
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461502
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
726986
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 19, 2024The c.272A>G (p.D91G) 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 272, causing the aspartic acid (D) at amino acid position 91 to be replaced by a glycine (G). 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
0.092
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0043
T;.;T
Eigen
Benign
0.083
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.81
T;T;.
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;M;M
MutationTaster
Benign
0.97
D;D;D;D
PrimateAI
Uncertain
0.48
T
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.016
Sift
Benign
0.095
T;T;T
Sift4G
Benign
0.14
T;T;T
Polyphen
0.0030
B;.;B
Vest4
0.14
MVP
0.17
MPC
0.13
ClinPred
0.38
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.14
gMVP
0.31

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: rs149607255; hg19: chr2-64778880; API