6-30580518-A-G

Position:

• chr6-30580518-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025091.2(ABCF1):​c.677A>G​(p.Gln226Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCF1 NM_001025091.2 missense, splice_region
• Scores: Splicing: ADA: 0.9168
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100524455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF1	NM_001025091.2	c.677A>G	p.Gln226Arg	missense_variant, splice_region_variant	8/25	ENST00000326195.13	NP_001020262.1
ABCF1	NM_001090.3	c.677A>G	p.Gln226Arg	missense_variant, splice_region_variant	8/24		NP_001081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13	c.677A>G	p.Gln226Arg	missense_variant, splice_region_variant	8/25	1	NM_001025091.2	ENSP00000313603	A1
ABCF1	ENST00000376545.7	c.677A>G	p.Gln226Arg	missense_variant, splice_region_variant	8/24	1		ENSP00000365728
ABCF1	ENST00000441867.6	c.680A>G	p.Gln227Arg	missense_variant, splice_region_variant	8/25	5		ENSP00000405512	P3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.677A>G (p.Q226R) alteration is located in exon 8 (coding exon 8) of the ABCF1 gene. This alteration results from a A to G substitution at nucleotide position 677, causing the glutamine (Q) at amino acid position 226 to be replaced by an arginine (R). 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	0.076
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.050	T;.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.095	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.77	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.15	B;.;.
Vest4		0.077
MutPred		0.25		Gain of MoRF binding (P = 0.0269);Gain of MoRF binding (P = 0.0269);.;
MVP		0.69
MPC		0.78
ClinPred		0.19	T
GERP RS		3.8
Varity_R		0.018
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.92
dbscSNV1_RF	Benign	0.71
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30548295; COSMIC: COSV58230778; COSMIC: COSV58230778;