17-7341984-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014716.4(ACAP1):c.148C>T(p.Arg50Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
ACAP1
NM_014716.4 missense
NM_014716.4 missense
Scores
4
5
10
Clinical Significance
Conservation
PhyloP100: 1.75
Genes affected
ACAP1 (HGNC:16467): (ArfGAP with coiled-coil, ankyrin repeat and PH domains 1) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in protein transport and regulation of catalytic activity. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACAP1 | NM_014716.4 | c.148C>T | p.Arg50Cys | missense_variant | 3/22 | ENST00000158762.8 | |
ACAP1 | XM_047437152.1 | c.148C>T | p.Arg50Cys | missense_variant | 3/18 | ||
ACAP1 | XM_047437150.1 | c.-75C>T | 5_prime_UTR_variant | 3/22 | |||
ACAP1 | XM_047437151.1 | c.-75C>T | 5_prime_UTR_variant | 2/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACAP1 | ENST00000158762.8 | c.148C>T | p.Arg50Cys | missense_variant | 3/22 | 1 | NM_014716.4 | P1 | |
ACAP1 | ENST00000570457.6 | c.-75C>T | 5_prime_UTR_variant | 3/8 | 5 | ||||
ACAP1 | ENST00000575425.1 | c.-75C>T | 5_prime_UTR_variant | 2/5 | 3 | ||||
ACAP1 | ENST00000576628.1 | n.286C>T | non_coding_transcript_exon_variant | 3/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152156Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251440Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135894
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727242
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74330
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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 | Feb 27, 2024 | The c.148C>T (p.R50C) alteration is located in exon 3 (coding exon 3) of the ACAP1 gene. This alteration results from a C to T substitution at nucleotide position 148, causing the arginine (R) at amino acid position 50 to be replaced by a cysteine (C). 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
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
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