NM_145298.6:c.280A>C

Variant names:

• chr22-39045049-A-C
• rs556837667
• NM_145298.6:c.280A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145298.6(APOBEC3F):​c.280A>C​(p.Thr94Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T94A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: APOBEC3F NM_145298.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145298.6. 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
	APOBEC3F	NM_145298.6	MANE Select	c.280A>C	p.Thr94Pro	missense	Exon 3 of 7	NP_660341.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3F	ENST00000308521.10	TSL:1 MANE Select	c.280A>C	p.Thr94Pro	missense	Exon 3 of 7	ENSP00000309749.5	Q8IUX4-1
	APOBEC3F	ENST00000911511.1		c.171+1959A>C		intron	N/A	ENSP00000581570.1
	APOBEC3F	ENST00000491387.1	TSL:4	n.427A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T
Eigen	Benign	0.043
Eigen_PC	Benign	-0.056
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.054	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.95	P
Vest4		0.31
MutPred		0.71		Gain of catalytic residue at T94 (P = 0.0441)
MVP		0.74
MPC		0.75
ClinPred		0.75	D
GERP RS		2.3
Varity_R		0.83
gMVP		0.46
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs556837667; hg19: chr22-39441054;