22-35726300-C-G

Variant names:

• chr22-35726300-C-G
• NM_030642.1:c.232C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030642.1(APOL5):​c.232C>G​(p.Leu78Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL5 NM_030642.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.277

Genes affected

APOL5 (HGNC:14869): (apolipoprotein L5) This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids or allow the binding of lipids to organelles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21092233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL5	NM_030642.1	c.232C>G	p.Leu78Val	missense_variant	Exon 3 of 5	ENST00000249044.2	NP_085145.1
APOL5	XM_006724321.5	c.184C>G	p.Leu62Val	missense_variant	Exon 4 of 6		XP_006724384.1
APOL5	XM_017028945.3	c.16C>G	p.Leu6Val	missense_variant	Exon 3 of 5		XP_016884434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL5	ENST00000249044.2	c.232C>G	p.Leu78Val	missense_variant	Exon 3 of 5	1	NM_030642.1	ENSP00000249044.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232C>G (p.L78V) alteration is located in exon 3 (coding exon 3) of the APOL5 gene. This alteration results from a C to G substitution at nucleotide position 232, causing the leucine (L) at amino acid position 78 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.8
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.077
Sift	Benign	0.14	T
Sift4G	Uncertain	0.024	D
Polyphen		0.97	D
Vest4		0.10
MutPred		0.58		Gain of helix (P = 0.0496);
MVP		0.11
MPC		0.26
ClinPred		0.27	T
GERP RS		-1.7
Varity_R		0.12
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36122347;