22-36199331-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001386885.1(APOL4):​c.81A>C​(p.Gln27His) variant causes a missense, splice region 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. 12/15 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Consequence

APOL4
NM_001386885.1 missense, splice_region

Scores

1
14

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.084607035).
BP6
Variant 22-36199331-T-G is Benign according to our data. Variant chr22-36199331-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3128037.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APOL4NM_001386885.1 linkuse as main transcriptc.81A>C p.Gln27His missense_variant, splice_region_variant 2/4 ENST00000683024.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APOL4ENST00000683024.1 linkuse as main transcriptc.81A>C p.Gln27His missense_variant, splice_region_variant 2/4 NM_001386885.1 P2Q9BPW4-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsDec 18, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
3.8
DANN
Benign
0.29
DEOGEN2
Benign
0.077
T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.036
N
LIST_S2
Benign
0.31
.;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.085
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PROVEAN
Pathogenic
-6.0
D;D
REVEL
Benign
0.069
Vest4
0.16
MutPred
0.13
Loss of ubiquitination at K45 (P = 0.0022);Loss of ubiquitination at K45 (P = 0.0022);
MVP
0.040
ClinPred
0.39
T
GERP RS
-0.35

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36595377; API