Genetic Variant NM_018358.3:c.206A>G (chr3-184186639-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_018358.3(ABCF3):c.206A>G(p.Tyr69Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ABCF3
NM_018358.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.71

Publications

2 publications found

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]

ABCF3 links:

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ACMG classification

Classification was made for transcript

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 link	c.206A>G	p.Tyr69Cys	missense_variant	Exon 2 of 21	ENST00000429586.7	NP_060828.2	Q9NUQ8-1A0A0S2Z5L1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCF3	ENST00000429586.7 link	c.206A>G	p.Tyr69Cys	missense_variant	Exon 2 of 21	1	NM_018358.3	ENSP00000411471.2		Q9NUQ8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458436

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725288

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33440

American (AMR)

AF:

0.00

AC:

AN:

44416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25804

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

85716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1110114

Other (OTH)

AF:

0.00

AC:

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 14, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.206A>G (p.Y69C) alteration is located in exon 2 (coding exon 2) of the ABCF3 gene. This alteration results from a A to G substitution at nucleotide position 206, causing the tyrosine (Y) at amino acid position 69 to be replaced by a cysteine (C). 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

0.19

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.72

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

1.1

PhyloP100

2.7

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.63

Sift

Benign

0.065

Sift4G

Benign

0.15

Polyphen

0.77

Vest4

0.58

MVP

0.96

MPC

0.69

ClinPred

0.77

GERP RS

4.0

PromoterAI

0.22

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.39

Mutation Taster

=0/100

disease causing

(source)

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

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NM_018358.3:c.206A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over