chrX-85087590-G-T

Position:

• chrX-85087590-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198450.6(APOOL):​c.719G>T​(p.Gly240Val) 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. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: APOOL NM_198450.6 missense, splice_region
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

Genes affected

APOOL (HGNC:24009): (apolipoprotein O like) This gene encodes a protein which contains an apolipoprotein O superfamily domain. This domain is found on proteins in circulating lipoprotein complexes. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOOL	NM_198450.6	c.719G>T	p.Gly240Val	missense_variant, splice_region_variant	9/9	ENST00000373173.7	NP_940852.3
APOOL	XM_017029272.2	c.728G>T	p.Gly243Val	missense_variant, splice_region_variant	9/9		XP_016884761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOOL	ENST00000373173.7	c.719G>T	p.Gly240Val	missense_variant, splice_region_variant	9/9	1	NM_198450.6	ENSP00000362268	P1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 21

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2023

The c.719G>T (p.G240V) alteration is located in exon 9 (coding exon 9) of the APOOL gene. This alteration results from a G to T substitution at nucleotide position 719, causing the glycine (G) at amino acid position 240 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.;T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-0.32	T
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.94	N;.;.
REVEL	Benign	0.18
Sift	Uncertain	0.017	D;.;.
Sift4G	Uncertain	0.059	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.28
MutPred		0.17		Gain of sheet (P = 0.0125);.;Gain of sheet (P = 0.0125);
MVP		0.61
MPC		0.050
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.98
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-84342596; COSMIC: COSV100261026; COSMIC: COSV100261026;