6-30579971-A-G

Variant names:

• chr6-30579971-A-G
• NM_001025091.2:c.530A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001025091.2(ABCF1):​c.530A>G​(p.Lys177Arg) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: ABCF1 NM_001025091.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.100875854).
• BP6: Variant 6-30579971-A-G is Benign according to our data. Variant chr6-30579971-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3882408.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025091.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCF1	NM_001025091.2	MANE Select	c.530A>G	p.Lys177Arg	missense	Exon 7 of 25	NP_001020262.1	A0A1U9X609
	ABCF1	NM_001090.3		c.530A>G	p.Lys177Arg	missense	Exon 7 of 24	NP_001081.1	Q2L6I2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCF1	ENST00000326195.13	TSL:1 MANE Select	c.530A>G	p.Lys177Arg	missense	Exon 7 of 25	ENSP00000313603.8	Q8NE71-1
	ABCF1	ENST00000376545.7	TSL:1	c.530A>G	p.Lys177Arg	missense	Exon 7 of 24	ENSP00000365728.3	Q8NE71-2
	ABCF1	ENST00000915359.1		c.533A>G	p.Lys178Arg	missense	Exon 7 of 25	ENSP00000585418.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.030
Sift	Benign	0.065	T
Sift4G	Benign	0.23	T
Polyphen		0.0060	B
Vest4		0.15
MutPred		0.12		Loss of glycosylation at K177 (P = 0.0271)
MVP		0.69
MPC		0.053
ClinPred		0.056	T
GERP RS		3.1
Varity_R		0.035
gMVP		0.013
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr6-30547748;