3-184188314-C-A

Variant summary

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

The NM_018358.3(ABCF3):​c.743C>A​(p.Thr248Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ABCF3
NM_018358.3 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90
Variant links:
Genes affected
ABCF3 (HGNC:72): (ATP binding cassette subfamily F member 3) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ATP-binding cassette proteins transport various molecules across extra- and intracellular membranes. The protein encoded by this gene displays antiviral effect against flaviviruses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

Genome browser will be placed here

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, 0.756

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCF3NM_018358.3 linkuse as main transcriptc.743C>A p.Thr248Asn missense_variant 7/21 ENST00000429586.7 NP_060828.2 Q9NUQ8-1A0A0S2Z5L1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCF3ENST00000429586.7 linkuse as main transcriptc.743C>A p.Thr248Asn missense_variant 7/211 NM_018358.3 ENSP00000411471.2 Q9NUQ8-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251256
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461772
Hom.:
0
Cov.:
33
AF XY:
0.00000413
AC XY:
3
AN XY:
727186
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 05, 2023The c.743C>A (p.T248N) alteration is located in exon 7 (coding exon 7) of the ABCF3 gene. This alteration results from a C to A substitution at nucleotide position 743, causing the threonine (T) at amino acid position 248 to be replaced by an asparagine (N). 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
0.36
BayesDel_addAF
Benign
0.0016
T
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.69
D;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Pathogenic
0.76
D;D
MetaSVM
Pathogenic
0.92
D
MutationAssessor
Benign
1.1
L;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-4.6
D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
0.76
P;D
Vest4
0.76
MutPred
0.39
Loss of sheet (P = 0.0054);.;
MVP
0.99
MPC
0.99
ClinPred
0.91
D
GERP RS
5.1
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.67
gMVP
0.66

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: rs754647500; hg19: chr3-183906102; API