rs1446997257

Variant names:

• chr22-35658902-G-T
• rs1446997257
• NM_030641.4:c.338G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-35658902-G-T
• chr22-35658902-G-C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_030641.4(APOL6):​c.338G>T​(p.Gly113Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL6 NM_030641.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

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.338G>T	p.Gly113Val	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.338G>T	p.Gly113Val	missense	Exon 3 of 3	ENSP00000386280.3	Q9BWW8
	APOL6	ENST00000958488.1		c.338G>T	p.Gly113Val	missense	Exon 4 of 4	ENSP00000628547.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250374 AF XY: 0.00

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: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.53
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	0.12
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.98	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		3.8
PrimateAI	Benign	0.34	T
PROVEAN	Pathogenic	-8.1	D
REVEL	Uncertain	0.29
Sift	Benign	0.041	D
Sift4G	Benign	0.085	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.96		Loss of disorder (P = 0.0281)
MVP		0.67
MPC		0.74
ClinPred		0.94	D
GERP RS		3.1
Varity_R		0.44
gMVP		0.84
Mutation Taster		=98/2	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: rs1446997257; hg19: chr22-36054949;