3-184186572-C-G

Variant names:

• chr3-184186572-C-G
• NM_018358.3:c.139C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018358.3(ABCF3):​c.139C>G​(p.Leu47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCF3 NM_018358.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15541765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCF3	NM_018358.3	c.139C>G	p.Leu47Val	missense_variant	Exon 2 of 21	ENST00000429586.7	NP_060828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCF3	ENST00000429586.7	c.139C>G	p.Leu47Val	missense_variant	Exon 2 of 21	1	NM_018358.3	ENSP00000411471.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.139C>G (p.L47V) alteration is located in exon 2 (coding exon 2) of the ABCF3 gene. This alteration results from a C to G substitution at nucleotide position 139, causing the leucine (L) at amino acid position 47 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	0.0074	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.074	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.35	N;N
PhyloP100		1.9
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.57	N;N
REVEL	Benign	0.24
Sift	Benign	0.25	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0010	B;B
Vest4		0.36
MutPred		0.47		Loss of glycosylation at S52 (P = 0.0618);Loss of glycosylation at S52 (P = 0.0618);
MVP		0.88
MPC		0.27
ClinPred		0.52	D
GERP RS		4.5
PromoterAI		0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.16
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

hg19: chr3-183904360;