Genetic Variant NM_018358.3:c.187G>T (chr3-184186620-G-T) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018358.3(ABCF3):c.187G>T(p.Ala63Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A63T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ABCF3
NM_018358.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.91

Publications

0 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCF3	NM_018358.3 link	c.187G>T	p.Ala63Ser	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.187G>T	p.Ala63Ser	missense_variant	Exon 2 of 21	1	NM_018358.3	ENSP00000411471.2		Q9NUQ8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460916

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726694

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111510

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

0.0073

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.072

MetaRNN

Benign

0.24

T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.0

N;N

PhyloP100

6.9

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.70

N;N

REVEL

Uncertain

0.34

Sift

Benign

0.71

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0040

B;B

Vest4

0.40

MutPred

0.27

Gain of disorder (P = 0.0373);Gain of disorder (P = 0.0373);

MVP

0.86

MPC

0.25

ClinPred

0.82

GERP RS

5.4

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.065

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.99

Position offset: -2

DS_DL_spliceai

0.31

Position offset: 34

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_018358.3:c.187G>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over