NM_001025091.2:c.2275C>G

Variant names:

• chr6-30590190-C-G
• rs754981516
• NM_001025091.2:c.2275C>G

Variant summary

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

The NM_001025091.2(ABCF1):​c.2275C>G​(p.Arg759Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R759W) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCF1 NM_001025091.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43
• Publications: 2 publications found

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]

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
ABCF1	NM_001025091.2	c.2275C>G	p.Arg759Gly	missense_variant	Exon 23 of 25	ENST00000326195.13	NP_001020262.1
ABCF1	NM_001090.3	c.2161C>G	p.Arg721Gly	missense_variant	Exon 22 of 24		NP_001081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13	c.2275C>G	p.Arg759Gly	missense_variant	Exon 23 of 25	1	NM_001025091.2	ENSP00000313603.8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.093	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.10	N;.
PhyloP100		2.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.0	N;N
REVEL	Uncertain	0.55
Sift	Benign	0.14	T;T
Sift4G	Benign	0.39	T;T
Polyphen		0.0050	B;.
Vest4		0.84
MutPred		0.43		Loss of methylation at R759 (P = 0.0395);.;
MVP		0.93
MPC		0.92
ClinPred		0.36	T
GERP RS		4.5
Varity_R		0.87
gMVP		0.73
Mutation Taster		=34/66	disease causing

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: rs754981516; hg19: chr6-30557967;