3-184186569-G-A

Variant names:

• chr3-184186569-G-A
• rs779378473
• NM_018358.3:c.136G>A

Variant summary

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

The NM_018358.3(ABCF3):​c.136G>A​(p.Glu46Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E46Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ABCF3 NM_018358.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.70
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCF3	NM_018358.3	c.136G>A	p.Glu46Lys	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.136G>A	p.Glu46Lys	missense_variant	Exon 2 of 21	1	NM_018358.3	ENSP00000411471.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461754 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727180

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111940

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.9	L;L
PhyloP100		8.7
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.3	N;N
REVEL	Uncertain	0.53
Sift	Benign	0.20	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.59	P;P
Vest4		0.56
MutPred		0.43		Gain of methylation at E46 (P = 0.0121);Gain of methylation at E46 (P = 0.0121);
MVP		0.93
MPC		0.40
ClinPred		0.97	D
GERP RS		4.5
PromoterAI		-0.0035	Neutral
Varity_R		0.53
gMVP		0.34
Mutation Taster		=86/14	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

dbSNP: rs779378473; hg19: chr3-183904357;