3-184186569-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018358.3(ABCF3):ā€‹c.136G>Cā€‹(p.Glu46Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000454 in 1,614,098 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‘“ 0.00012 ( 0 hom., cov: 32)
Exomes š‘“: 0.00049 ( 0 hom. )

Consequence

ABCF3
NM_018358.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.70
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28909004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCF3NM_018358.3 linkc.136G>C p.Glu46Gln missense_variant 2/21 ENST00000429586.7 NP_060828.2 Q9NUQ8-1A0A0S2Z5L1
ABCF3NM_001351298.2 linkc.136G>C p.Glu46Gln missense_variant 2/21 NP_001338227.1
ABCF3NM_001351300.2 linkc.-561G>C 5_prime_UTR_variant 2/21 NP_001338229.1
ABCF3NM_001351299.2 linkc.-601G>C 5_prime_UTR_variant 2/22 NP_001338228.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCF3ENST00000429586.7 linkc.136G>C p.Glu46Gln missense_variant 2/211 NM_018358.3 ENSP00000411471.2 Q9NUQ8-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000127
AC:
32
AN:
251234
Hom.:
0
AF XY:
0.000118
AC XY:
16
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000488
AC:
713
AN:
1461754
Hom.:
0
Cov.:
34
AF XY:
0.000472
AC XY:
343
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
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:
0.000629
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152344
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000670
Hom.:
0
Bravo
AF:
0.000128
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00104
AC:
4
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.000273
EpiControl
AF:
0.000237

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 GeneticsAug 26, 2024The c.136G>C (p.E46Q) alteration is located in exon 2 (coding exon 2) of the ABCF3 gene. This alteration results from a G to C substitution at nucleotide position 136, causing the glutamic acid (E) at amino acid position 46 to be replaced by a glutamine (Q). 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
0.15
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.12
T;.
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.060
D
MetaRNN
Benign
0.29
T;T
MetaSVM
Uncertain
0.24
D
MutationAssessor
Benign
1.9
L;L
PrimateAI
Uncertain
0.70
T
PROVEAN
Benign
-0.88
N;N
REVEL
Uncertain
0.42
Sift
Benign
0.20
T;T
Sift4G
Benign
0.26
T;T
Polyphen
0.38
B;P
Vest4
0.49
MVP
0.92
MPC
0.30
ClinPred
0.19
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.22

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: rs779378473; hg19: chr3-183904357; API