22-35656459-G-A

Variant names:

• chr22-35656459-G-A
• rs778101319
• NM_030641.4:c.34G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030641.4(APOL6):​c.34G>A​(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: APOL6 NM_030641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.220
• Publications: 1 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.34G>A	p.Gly12Ser	missense	Exon 2 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.34G>A	p.Gly12Ser	missense	Exon 2 of 3	ENSP00000386280.3	Q9BWW8
	APOL6	ENST00000958488.1		c.34G>A	p.Gly12Ser	missense	Exon 3 of 4	ENSP00000628547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251374 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461820 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111958

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.22
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.069
Sift	Benign	0.063	T
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.056
MutPred		0.36		Gain of phosphorylation at G12 (P = 0.0132)
MVP		0.23
MPC		0.56
ClinPred		0.41	T
GERP RS		2.4
Varity_R		0.022
gMVP		0.14
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.42		Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs778101319; hg19: chr22-36052506; COSMIC: COSV68749814;