rs753777961

Variant names:

• chr22-39025112-T-C
• rs753777961
• NM_152426.4:c.253T>C

Variant summary

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

The NM_152426.4(APOBEC3D):​c.253T>C​(p.Ser85Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: APOBEC3D NM_152426.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.824
• Publications: 0 publications found

Genes affected

APOBEC3D (HGNC:17354): (apolipoprotein B mRNA editing enzyme catalytic subunit 3D) This gene is a member of the cytidine deaminase gene family. It is one of a group of related genes 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 and inhibit retroviruses, such as HIV, by deaminating cytosine residues in nascent retroviral cDNA. [provided by RefSeq, Jul 2008]

ENSG00000284554 (HGNC:):

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_152426.4. 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
	APOBEC3D	NM_152426.4	MANE Select	c.253T>C	p.Ser85Pro	missense	Exon 3 of 7	NP_689639.2	Q96AK3
	APOBEC3D	NM_001363781.1		c.210+2098T>C		intron	N/A	NP_001350710.1	Q6ICH2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC3D	ENST00000216099.13	TSL:2 MANE Select	c.253T>C	p.Ser85Pro	missense	Exon 3 of 7	ENSP00000216099.7	Q96AK3
	ENSG00000284554	ENST00000381568.9	TSL:1	c.253T>C	p.Ser85Pro	missense	Exon 3 of 7	ENSP00000370980.4
	APOBEC3D	ENST00000427494.6	TSL:1	c.210+2098T>C		intron	N/A	ENSP00000388017.2	Q6ICH2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248734 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1458404 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 725136

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.00 AC: 0 AN: 86024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1109654

Other (OTH) AF: 0.00 AC: 0 AN: 60218

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	6.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.82
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.25
Sift	Benign	0.14	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.68		Gain of catalytic residue at W86 (P = 0.0738)
MVP		0.40
MPC		0.33
ClinPred		0.18	T
GERP RS		-1.7
Varity_R		0.16
gMVP		0.73
Mutation Taster		=98/2	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: rs753777961; hg19: chr22-39421117;