chr22-36191892-T-G

Variant names:

• chr22-36191892-T-G
• rs758551863
• NM_001386885.1:c.230A>C

Variant summary

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

The NM_001386885.1(APOL4):​c.230A>C​(p.Tyr77Ser) 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. 12/19 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. Y77C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APOL4 NM_001386885.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.36
• 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=0.14219138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL4	NM_001386885.1	c.230A>C	p.Tyr77Ser	missense_variant	Exon 4 of 4	ENST00000683024.1	NP_001373814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL4	ENST00000683024.1	c.230A>C	p.Tyr77Ser	missense_variant	Exon 4 of 4		NM_001386885.1	ENSP00000507418.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.10
DANN	Benign	0.80
DEOGEN2	Benign	0.028	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.46	T;.;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.95	T
PhyloP100		-4.4
PROVEAN	Uncertain	-2.4	N;.;N
REVEL	Benign	0.066
Sift	Benign	0.20	T;.;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.26	B;.;.
Vest4		0.17
MutPred		0.58		Gain of disorder (P = 0.0054);.;.;
MVP		0.061
MPC		0.51
ClinPred		0.25	T
GERP RS		-3.2
Varity_R		0.16
gMVP		0.26
Mutation Taster		=97/3	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: rs758551863; hg19: chr22-36587938;