chr2-64551985-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_203437.4(AFTPH):​c.511T>C​(p.Cys171Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

AFTPH
NM_203437.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.60
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AFTPHNM_203437.4 linkuse as main transcriptc.511T>C p.Cys171Arg missense_variant 2/10 ENST00000409933.6 NP_982261.2
LOC105374773XR_007086343.1 linkuse as main transcriptn.5406-721A>G 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.511T>C p.Cys171Arg missense_variant 2/101 NM_203437.4 ENSP00000387071 A1Q6ULP2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 GeneticsSep 06, 2022The c.511T>C (p.C171R) alteration is located in exon 2 (coding exon 1) of the AFTPH gene. This alteration results from a T to C substitution at nucleotide position 511, causing the cysteine (C) at amino acid position 171 to be replaced by an arginine (R). 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
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.25
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
T;.;T
Eigen
Uncertain
0.67
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.78
T;T;.
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.76
D;D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.6
M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-4.1
D;D;D
REVEL
Uncertain
0.53
Sift
Pathogenic
0.0
D;D;D
Sift4G
Benign
0.094
T;D;T
Polyphen
1.0
D;.;D
Vest4
0.82
MutPred
0.64
Gain of disorder (P = 0.0514);Gain of disorder (P = 0.0514);Gain of disorder (P = 0.0514);
MVP
0.51
MPC
0.65
ClinPred
1.0
D
GERP RS
5.8
Varity_R
0.92
gMVP
0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-64779119; API