7-151223994-A-C

Position:

• chr7-151223994-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_007189.3(ABCF2):​c.488T>G​(p.Met163Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ABCF2 NM_007189.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.01

Genes affected

ABCF2 (HGNC:71): (ATP binding cassette subfamily F member 2) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. ATP-binding cassette proteins transport various molecules across extra- and intracellular membranes. Alterations in this gene may be involved in cancer progression. Related pseudogenes have been identified on chromosomes 3 and 7. [provided by RefSeq, Mar 2019]

ABCF2-H2BK1 (HGNC:54751): (ABCF2-H2BK1 readthrough) This gene represents readthrough transcription between ABCF2 and a downstream histone H2B-like gene. [provided by RefSeq, Mar 2019]

ABCF2-H2BK1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF2	NM_007189.3	c.488T>G	p.Met163Arg	missense_variant	4/15	ENST00000287844.7	NP_009120.1
ABCF2-H2BK1	NM_005692.5	c.488T>G	p.Met163Arg	missense_variant	4/16		NP_005683.2
ABCF2-H2BK1	NR_160983.1	n.573T>G		non_coding_transcript_exon_variant	4/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF2	ENST00000287844.7	c.488T>G	p.Met163Arg	missense_variant	4/15	1	NM_007189.3	ENSP00000287844.2
ABCF2-H2BK1	ENST00000222388.6	c.488T>G	p.Met163Arg	missense_variant	4/16	5		ENSP00000222388.2
ABCF2	ENST00000468073.5	c.488T>G	p.Met163Arg	missense_variant	3/6	2		ENSP00000419720.1
ABCF2	ENST00000441774.1	c.488T>G	p.Met163Arg	missense_variant	4/5	3		ENSP00000395785.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

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

Mar 15, 2024

The c.488T>G (p.M163R) alteration is located in exon 4 (coding exon 3) of the ABCF2 gene. This alteration results from a T to G substitution at nucleotide position 488, causing the methionine (M) at amino acid position 163 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	Pathogenic	0.77
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.59	.;D;.;.
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	0.78	.;N;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-4.1	D;D;D;D
REVEL	Pathogenic	0.70
Sift	Benign	0.21	T;T;T;D
Sift4G	Benign	0.17	T;T;.;T
Polyphen		0.83	.;P;.;.
Vest4		0.98
MutPred		0.62		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.99
MPC		1.7
ClinPred		0.95	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.69
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1802325092; hg19: chr7-150921080;