22-35720618-G-T

Variant names:

• chr22-35720618-G-T
• NM_030642.1:c.106G>T

Variant summary

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

The NM_030642.1(APOL5):​c.106G>T​(p.Gly36Cys) 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. 14/21 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: 0.120

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=0.14982364).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL5	NM_030642.1	c.106G>T	p.Gly36Cys	missense_variant	Exon 2 of 5	ENST00000249044.2	NP_085145.1
APOL5	XM_006724321.5	c.155+13G>T		intron_variant	Intron 3 of 5		XP_006724384.1
APOL5	XM_017028945.3	c.-13-5654G>T		intron_variant	Intron 2 of 4		XP_016884434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL5	ENST00000249044.2	c.106G>T	p.Gly36Cys	missense_variant	Exon 2 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

Nov 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106G>T (p.G36C) alteration is located in exon 2 (coding exon 2) of the APOL5 gene. This alteration results from a G to T substitution at nucleotide position 106, causing the glycine (G) at amino acid position 36 to be replaced by a cysteine (C). 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	0.15
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.16
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.28
MutPred		0.45		Loss of sheet (P = 0.0315);
MVP		0.25
MPC		0.75
ClinPred		0.67	D
GERP RS		-2.6
Varity_R		0.26
gMVP		0.086

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: chr22-36116665;