rs143660228

Variant names:

• chr22-35658815-C-G
• rs143660228
• NM_030641.4:c.251C>G

Your query was ambiguous. Multiple possible variants found:

• chr22-35658815-C-G
• chr22-35658815-C-T

Variant summary

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

The NM_030641.4(APOL6):​c.251C>G​(p.Thr84Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. T84I) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: APOL6 NM_030641.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09152827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL6	NM_030641.4	c.251C>G	p.Thr84Ser	missense_variant	Exon 3 of 3	ENST00000409652.5	NP_085144.1
APOL6	XM_011530392.4	c.251C>G	p.Thr84Ser	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.251C>G	p.Thr84Ser	missense_variant	Exon 3 of 3	1	NM_030641.4	ENSP00000386280.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.0
DANN	Benign	0.61
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.048
Sift	Benign	0.18	T
Sift4G	Benign	0.21	T
Polyphen		0.20	B
Vest4		0.088
MutPred		0.47		Loss of glycosylation at S83 (P = 0.071);
MVP		0.19
MPC		0.20
ClinPred		0.13	T
GERP RS		-2.2
Varity_R		0.057
gMVP		0.40

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

LitVar

Other links and lift over

dbSNP: rs143660228; hg19: chr22-36054862;