1-183648231-A-G

Variant names:

• chr1-183648231-A-G
• NM_203454.3:c.551T>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_203454.3(APOBEC4):​c.551T>C​(p.Val184Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.22
• Publications: 0 publications found

Genes affected

APOBEC4 (HGNC:32152): (apolipoprotein B mRNA editing enzyme catalytic polypeptide like 4) This gene encodes a member of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases, which convert cytidine to uridine. Other AID/APOBEC family members are involved in mRNA editing, somatic hypermutation and recombination of immunoglobulin genes, and innate immunity to retroviral infection. [provided by RefSeq, Jul 2008]

RGL1 (HGNC:30281): (ral guanine nucleotide dissociation stimulator like 1) Predicted to be involved in regulation of catalytic activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203454.3. 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
	APOBEC4	NM_203454.3	MANE Select	c.551T>C	p.Val184Ala	missense	Exon 2 of 2	NP_982279.1	Q8WW27
	RGL1	NM_015149.6		c.-33+11730A>G		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.-143+11730A>G		intron	N/A	NP_001284598.1	B7Z2W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOBEC4	ENST00000308641.6	TSL:1 MANE Select	c.551T>C	p.Val184Ala	missense	Exon 2 of 2	ENSP00000310622.4	Q8WW27
	RGL1	ENST00000304685.8	TSL:1	c.-33+11730A>G		intron	N/A	ENSP00000303192.3	Q9NZL6-2
	APOBEC4	ENST00000481562.1	TSL:3	n.246-434T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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	0.42
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.090	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.2
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.35		Loss of sheet (P = 0.0181)
MVP		0.34
MPC		0.53
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.75
gMVP		0.67
Mutation Taster		=85/15	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

hg19: chr1-183617366;