22-35658989-C-A

Variant names:

• chr22-35658989-C-A
• rs186819188
• NM_030641.4:c.425C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_030641.4(APOL6):​c.425C>A​(p.Ala142Glu) 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 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. A142V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL6 NM_030641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 3 publications found

Genes affected

APOL6 (HGNC:14870): (apolipoprotein L6) 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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030641.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL6	NM_030641.4	MANE Select	c.425C>A	p.Ala142Glu	missense	Exon 3 of 3	NP_085144.1	Q9BWW8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL6	ENST00000409652.5	TSL:1 MANE Select	c.425C>A	p.Ala142Glu	missense	Exon 3 of 3	ENSP00000386280.3	Q9BWW8
	APOL6	ENST00000958488.1		c.425C>A	p.Ala142Glu	missense	Exon 4 of 4	ENSP00000628547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0046	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		-0.076
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.14
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.40
MutPred		0.83		Gain of disorder (P = 0.0953)
MVP		0.32
MPC		0.73
ClinPred		0.88	D
GERP RS		-4.7
Varity_R		0.73
gMVP		0.91
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: rs186819188; hg19: chr22-36055036;