22-35658939-C-A

Variant names:

• chr22-35658939-C-A
• NM_030641.4:c.375C>A
• APOL6 p.Ile125Ile

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030641.4(APOL6):​c.375C>A​(p.Ile125Ile) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I125I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL6 NM_030641.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.95 with no splicing effect.

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.375C>A	p.Ile125Ile	synonymous	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.375C>A	p.Ile125Ile	synonymous	Exon 3 of 3	ENSP00000386280.3	Q9BWW8
	APOL6	ENST00000958488.1		c.375C>A	p.Ile125Ile	synonymous	Exon 4 of 4	ENSP00000628547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.11
DANN	Benign	0.49
PhyloP100		-0.95

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr22-36054986;