rs1189033247

Variant names:

• chr22-35658980-A-C
• NM_030641.4:c.416A>C

Your query was ambiguous. Multiple possible variants found:

• chr22-35658980-A-C
• chr22-35658980-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030641.4(APOL6):​c.416A>C​(p.Gln139Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. Q139R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOL6 NM_030641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34100658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL6	NM_030641.4	c.416A>C	p.Gln139Pro	missense_variant	Exon 3 of 3	ENST00000409652.5	NP_085144.1
APOL6	XM_011530392.4	c.416A>C	p.Gln139Pro	missense_variant	Exon 4 of 4		XP_011528694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL6	ENST00000409652.5	c.416A>C	p.Gln139Pro	missense_variant	Exon 3 of 3	1	NM_030641.4	ENSP00000386280.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727082

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.068
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.63		Gain of glycosylation at Q139 (P = 0.0296);
MVP		0.30
MPC		0.73
ClinPred		0.72	D
GERP RS		-0.88
Varity_R		0.79
gMVP		0.88

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: chr22-36055027;