7-151224832-G-C

Position:

• chr7-151224832-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3 BS2

The NM_007189.3(ABCF2):​c.311C>G​(p.Thr104Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ABCF2 NM_007189.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.66

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 Likely_benign. Variant got -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.749
• BS2: High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCF2	NM_007189.3	c.311C>G	p.Thr104Ser	missense_variant	3/15	ENST00000287844.7	NP_009120.1
ABCF2-H2BK1	NM_005692.5	c.311C>G	p.Thr104Ser	missense_variant	3/16		NP_005683.2
ABCF2-H2BK1	NR_160983.1	n.396C>G		non_coding_transcript_exon_variant	3/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCF2	ENST00000287844.7	c.311C>G	p.Thr104Ser	missense_variant	3/15	1	NM_007189.3	ENSP00000287844.2
ABCF2-H2BK1	ENST00000222388.6	c.311C>G	p.Thr104Ser	missense_variant	3/16	5		ENSP00000222388.2
ABCF2	ENST00000468073.5	c.311C>G	p.Thr104Ser	missense_variant	2/6	2		ENSP00000419720.1
ABCF2	ENST00000441774.1	c.311C>G	p.Thr104Ser	missense_variant	3/5	3		ENSP00000395785.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727248

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: 0.00000450

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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 23, 2023

The c.311C>G (p.T104S) alteration is located in exon 3 (coding exon 2) of the ABCF2 gene. This alteration results from a C to G substitution at nucleotide position 311, causing the threonine (T) at amino acid position 104 to be replaced by a serine (S). 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	0.19
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	.;T;.;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	0.85	.;L;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Uncertain	0.59
Sift	Benign	0.69	T;T;T;T
Sift4G	Benign	0.63	T;T;.;T
Polyphen		0.25	.;B;.;.
Vest4		0.67
MutPred		0.53		Gain of disorder (P = 0.0448);Gain of disorder (P = 0.0448);Gain of disorder (P = 0.0448);Gain of disorder (P = 0.0448);
MVP		0.91
MPC		1.0
ClinPred		0.65	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.66

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: rs762114784; hg19: chr7-150921918;