rs1046098637

Variant names:

• chr22-36195390-C-A
• NM_001386885.1:c.130G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36195390-C-A
• chr22-36195390-C-G
• chr22-36195390-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001386885.1(APOL4):​c.130G>T​(p.Val44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V44L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOL4 NM_001386885.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.8

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL4	NM_001386885.1	c.130G>T	p.Val44Phe	missense_variant	Exon 3 of 4	ENST00000683024.1	NP_001373814.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL4	ENST00000683024.1	c.130G>T	p.Val44Phe	missense_variant	Exon 3 of 4		NM_001386885.1	ENSP00000507418.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461504 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727042

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.2
DANN	Benign	0.50
DEOGEN2	Benign	0.014	T;.;.;.;.
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.51	T;.;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Benign	-0.73	T
PROVEAN	Uncertain	-2.9	D;.;D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.011	D;.;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;.
Polyphen		0.98	D;.;.;.;.
Vest4		0.26
MutPred		0.86		Gain of ubiquitination at K46 (P = 0.0872);.;.;.;.;
MVP		0.48
MPC		0.34
ClinPred		0.62	D
GERP RS		-4.1
Varity_R		0.10
gMVP		0.29

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36591436;