rs754981516

Positions:

• chr6-30590190-C-G
• chr6-30590190-C-T

Variant summary

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

The ENST00000326195.13(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 ENST00000326195.13 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.43

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

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13	c.2275C>G	p.Arg759Gly	missense_variant	23/25	1	NM_001025091.2	ENSP00000313603	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

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;.
MutationTaster	Benign	1.0	D;D;D
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

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

Other links and lift over

dbSNP: rs754981516; hg19: chr6-30557967;