Variant 6-30582455-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001025091.2(ABCF1):c.740A>G(p.Asp247Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,460,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ABCF1
NM_001025091.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Variant links:

Genes affected

ABCF1 (HGNC:70): (ATP binding cassette subfamily F member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process. [provided by RefSeq, Jul 2008]

ABCF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13856652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF1	NM_001025091.2 linkuse as main transcript	c.740A>G	p.Asp247Gly	missense_variant	9/25	ENST00000326195.13	NP_001020262.1
ABCF1	NM_001090.3 linkuse as main transcript	c.679-611A>G		intron_variant			NP_001081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13 linkuse as main transcript	c.740A>G	p.Asp247Gly	missense_variant	9/25	1	NM_001025091.2	ENSP00000313603	A1	Q8NE71-1
ABCF1	ENST00000376545.7 linkuse as main transcript	c.679-611A>G		intron_variant		1		ENSP00000365728		Q8NE71-2
ABCF1	ENST00000441867.6 linkuse as main transcript	c.743A>G	p.Asp248Gly	missense_variant	9/25	5		ENSP00000405512	P3
ABCF1	ENST00000475993.1 linkuse as main transcript			upstream_gene_variant		1		ENSP00000445100

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460718

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726682

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000126

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

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 submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.740A>G (p.D247G) alteration is located in exon 9 (coding exon 9) of the ABCF1 gene. This alteration results from a A to G substitution at nucleotide position 740, causing the aspartic acid (D) at amino acid position 247 to be replaced by a glycine (G). 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

0.087

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.023

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.75

D;D;D

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.057

Sift

Uncertain

0.028

D;D

Sift4G

Benign

0.34

T;D

Polyphen

0.022

B;.

Vest4

0.15

MutPred

0.24

Loss of stability (P = 0.0197);.;

MVP

0.74

MPC

0.95

ClinPred

0.48

GERP RS

5.1

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.15

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over