22-39045199-G-C

Variant names:

• chr22-39045199-G-C
• NM_145298.6:c.430G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145298.6(APOBEC3F):​c.430G>C​(p.Val144Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: APOBEC3F NM_145298.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.494

Genes affected

APOBEC3F (HGNC:17356): (apolipoprotein B mRNA editing enzyme catalytic subunit 3F) This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster, thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. It is thought that the proteins may be RNA editing enzymes and have roles in growth or cell cycle control. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14467832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOBEC3F	NM_145298.6	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 7	ENST00000308521.10	NP_660341.2
APOBEC3F	XM_047441184.1	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 6		XP_047297140.1
APOBEC3F	XM_047441185.1	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 5		XP_047297141.1
APOBEC3F	XM_017028642.3	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 5		XP_016884131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOBEC3F	ENST00000308521.10	c.430G>C	p.Val144Leu	missense_variant	Exon 3 of 7	1	NM_145298.6	ENSP00000309749.5
APOBEC3F	ENST00000476513.1	n.16G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3
APOBEC3F	ENST00000491387.1	n.*7G>C		downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461866 Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5 AN XY: 727234

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.430G>C (p.V144L) alteration is located in exon 3 (coding exon 3) of the APOBEC3F gene. This alteration results from a G to C substitution at nucleotide position 430, causing the valine (V) at amino acid position 144 to be replaced by a leucine (L). 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	Uncertain	0.39
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.7
DANN	Benign	0.94
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.2	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.053
Sift	Benign	0.10	T
Sift4G	Benign	0.33	T
Polyphen		0.33	B
Vest4		0.13
MutPred		0.65		Loss of MoRF binding (P = 0.1048);
MVP		0.24
MPC		1.1
ClinPred		0.20	T
GERP RS		-2.6
Varity_R		0.21
gMVP		0.066

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr22-39441204;