rs17853301

Positions:

• chr6-30579937-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_001025091.2(ABCF1):​c.496T>C​(p.Ser166Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,656 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ABCF1 NM_001025091.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30

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.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity ABCF1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.101242125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF1	NM_001025091.2	c.496T>C	p.Ser166Pro	missense_variant	7/25	ENST00000326195.13	NP_001020262.1
ABCF1	NM_001090.3	c.496T>C	p.Ser166Pro	missense_variant	7/24		NP_001081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF1	ENST00000326195.13	c.496T>C	p.Ser166Pro	missense_variant	7/25	1	NM_001025091.2	ENSP00000313603.8
ABCF1	ENST00000376545.7	c.496T>C	p.Ser166Pro	missense_variant	7/24	1		ENSP00000365728.3
ABCF1	ENST00000441867.6	c.499T>C	p.Ser167Pro	missense_variant	7/25	5		ENSP00000405512.2
ABCF1	ENST00000468958.1	c.205T>C	p.Ser69Pro	missense_variant	6/7	3		ENSP00000440893.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460656 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726654

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T;.;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.66	.;.;.;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.10	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.94	N;N;N;D
REVEL	Benign	0.052
Sift	Uncertain	0.0080	D;D;D;D
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.16	B;.;.;.
Vest4		0.35
MutPred		0.11		Loss of phosphorylation at S166 (P = 0.0145);Loss of phosphorylation at S166 (P = 0.0145);.;.;
MVP		0.76
MPC		0.11
ClinPred		0.14	T
GERP RS		3.1
Varity_R		0.057
gMVP		0.034

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: rs17853301; hg19: chr6-30547714;