chr7-151218591-T-G

Position:

• chr7-151218591-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_007189.3(ABCF2):​c.1197A>C​(p.Gln399His) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ABCF2 NM_007189.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.422

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ABCF2
• BP4: Computational evidence support a benign effect (MetaRNN=0.24063909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCF2	NM_007189.3	c.1197A>C	p.Gln399His	missense_variant	10/15	ENST00000287844.7
ABCF2-H2BK1	NR_160983.1	n.1282A>C		non_coding_transcript_exon_variant	10/17
ABCF2-H2BK1	NM_005692.5	c.1197A>C	p.Gln399His	missense_variant	10/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCF2	ENST00000287844.7	c.1197A>C	p.Gln399His	missense_variant	10/15	1	NM_007189.3	P1
ABCF2	ENST00000473874.1	n.586A>C		non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

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

Feb 15, 2023

The c.1197A>C (p.Q399H) alteration is located in exon 10 (coding exon 9) of the ABCF2 gene. This alteration results from a A to C substitution at nucleotide position 1197, causing the glutamine (Q) at amino acid position 399 to be replaced by a histidine (H). 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	0.93
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	17
DANN	Uncertain	0.98
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.68	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.40
Sift	Benign	0.10	T;T
Sift4G	Benign	0.15	T;T
Polyphen		0.0	.;B
Vest4		0.36
MutPred		0.43		Loss of catalytic residue at Q399 (P = 0.086);Loss of catalytic residue at Q399 (P = 0.086);
MVP		0.77
MPC		0.63
ClinPred		0.52	D
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.38
gMVP		0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150915677;