ENST00000352371.5:c.13G>C

Variant names:

• chr22-36202024-C-G
• ENST00000352371.5:c.13G>C
• APOL4 p.Ala5Pro

Variant summary

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

The ENST00000352371.5(APOL4):​c.13G>C​(p.Ala5Pro) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A5G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL4 ENST00000352371.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.467
• Publications: 0 publications found

Genes affected

APOL4 (HGNC:14867): (apolipoprotein L4) This gene encodes a member of the apolipoprotein L family. The encoded protein may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2020]

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=0.09830767).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000352371.5. 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
	APOL4	NM_145660.2		c.13G>C	p.Ala5Pro	missense	Exon 2 of 5	NP_663693.1	Q9BPW4-1
	APOL4	NM_030643.4		c.-186G>C		5_prime_UTR	Exon 2 of 6	NP_085146.2	Q9BPW4-2
	APOL4	NM_145661.2		c.-186G>C		5_prime_UTR	Exon 2 of 6	NP_663694.1	Q9BRG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL4	ENST00000352371.5	TSL:1	c.13G>C	p.Ala5Pro	missense	Exon 2 of 5	ENSP00000338260.3	Q9BPW4-1
	APOL4	ENST00000616056.4	TSL:1	c.-186G>C		5_prime_UTR	Exon 2 of 6	ENSP00000483497.1	Q9BPW4-2
	APOL4	ENST00000397275.6	TSL:1	c.-186G>C		5_prime_UTR	Exon 2 of 6	ENSP00000380445.2	Q9BRG6

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	Benign	0.28
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.1
DANN	Benign	0.84
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.47
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.046
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
PromoterAI		-0.084	Neutral
Varity_R		0.11
gMVP		0.15
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-36598070;