Variant 6-30583675-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001025091.2(ABCF1):c.983C>A(p.Ala328Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ABCF1
NM_001025091.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF1	NM_001025091.2 linkuse as main transcript	c.983C>A	p.Ala328Asp	missense_variant	11/25	ENST00000326195.13	NP_001020262.1
ABCF1	NM_001090.3 linkuse as main transcript	c.869C>A	p.Ala290Asp	missense_variant	10/24		NP_001081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13 linkuse as main transcript	c.983C>A	p.Ala328Asp	missense_variant	11/25	1	NM_001025091.2	ENSP00000313603	A1	Q8NE71-1
ABCF1	ENST00000376545.7 linkuse as main transcript	c.869C>A	p.Ala290Asp	missense_variant	10/24	1		ENSP00000365728		Q8NE71-2
ABCF1	ENST00000475993.1 linkuse as main transcript	c.236C>A	p.Ala79Asp	missense_variant, NMD_transcript_variant	3/18	1		ENSP00000445100
ABCF1	ENST00000441867.6 linkuse as main transcript	c.986C>A	p.Ala329Asp	missense_variant	11/25	5		ENSP00000405512	P3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461722

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727142

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

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

Jun 21, 2021

The c.983C>A (p.A328D) alteration is located in exon 11 (coding exon 11) of the ABCF1 gene. This alteration results from a C to A substitution at nucleotide position 983, causing the alanine (A) at amino acid position 328 to be replaced by an aspartic acid (D). 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

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.44

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.96

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

0.51

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.2

N;N;N

REVEL

Uncertain

0.61

Sift

Benign

0.20

T;T;D

Sift4G

Benign

0.21

T;T;T

Polyphen

0.25

B;.;.

Vest4

0.89

MutPred

0.45

Gain of solvent accessibility (P = 0.1422);.;.;

MVP

0.96

MPC

1.1

ClinPred

0.92

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.61

gMVP

0.85

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

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