chr22-36199331-T-G

Variant names:

• chr22-36199331-T-G
• NM_001386885.1:c.81A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001386885.1(APOL4):​c.81A>C​(p.Gln27His) variant causes a missense, splice region 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. 13/16 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: APOL4 NM_001386885.1 missense, splice_region
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0470
• Publications: 0 publications found

Genes affected

APOL4 (HGNC:14867): (apolipoprotein L4) This gene encodes a member of the apolipoprotein L family. The encoded protein may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2020]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084607035).
• BP6: Variant 22-36199331-T-G is Benign according to our data. Variant chr22-36199331-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3128037.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386885.1. 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
	APOL4	NM_001386885.1	MANE Select	c.81A>C	p.Gln27His	missense splice_region	Exon 2 of 4	NP_001373814.1	Q9BPW4-2
	APOL4	NM_145660.2		c.90A>C	p.Gln30His	missense splice_region	Exon 3 of 5	NP_663693.1	Q9BPW4-1
	APOL4	NM_030643.4		c.81A>C	p.Gln27His	missense splice_region	Exon 4 of 6	NP_085146.2	Q9BPW4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL4	ENST00000683024.1	MANE Select	c.81A>C	p.Gln27His	missense splice_region	Exon 2 of 4	ENSP00000507418.1	Q9BPW4-2
	APOL4	ENST00000352371.5	TSL:1	c.90A>C	p.Gln30His	missense splice_region	Exon 3 of 5	ENSP00000338260.3	Q9BPW4-1
	APOL4	ENST00000616056.4	TSL:1	c.81A>C	p.Gln27His	missense splice_region	Exon 4 of 6	ENSP00000483497.1	Q9BPW4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.22
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.8
DANN	Benign	0.29
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.047
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.069
Vest4		0.16
MutPred		0.13		Loss of ubiquitination at K45 (P = 0.0022)
MVP		0.040
ClinPred		0.39	T
GERP RS		-0.35
Varity_R		0.030
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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

hg19: chr22-36595377;