chr1-183647836-T-A

Variant names:

• chr1-183647836-T-A
• rs542021279
• NM_203454.3:c.946A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203454.3(APOBEC4):​c.946A>T​(p.Ile316Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 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. I316L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOBEC4 NM_203454.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09325498).

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.946A>T	p.Ile316Phe	missense	Exon 2 of 2	NP_982279.1	Q8WW27
	RGL1	NM_015149.6		c.-33+11335T>A		intron	N/A	NP_055964.3
	RGL1	NM_001297669.3		c.-143+11335T>A		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.946A>T	p.Ile316Phe	missense	Exon 2 of 2	ENSP00000310622.4	Q8WW27
	RGL1	ENST00000304685.8	TSL:1	c.-33+11335T>A		intron	N/A	ENSP00000303192.3	Q9NZL6-2
	APOBEC4	ENST00000481562.1	TSL:3	n.246-39A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 32

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	Benign	0.21
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.8
DANN	Benign	0.79
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.046
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.039
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.011	D
Polyphen		0.43	B
Vest4		0.21
MutPred		0.22		Loss of MoRF binding (P = 0.0946)
MVP		0.092
MPC		0.28
ClinPred		0.47	T
GERP RS		-0.73
Varity_R		0.21
gMVP		0.29
Mutation Taster		=91/9	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: rs542021279; hg19: chr1-183616971;