chrX-85074383-C-A

Position:

• chrX-85074383-C-A

Variant summary

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

The NM_198450.6(APOOL):​c.710C>A​(p.Ser237Tyr) variant causes a missense 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. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: APOOL NM_198450.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.734

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09628573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOOL	NM_198450.6	c.710C>A	p.Ser237Tyr	missense_variant	8/9	ENST00000373173.7	NP_940852.3
APOOL	XM_017029272.2	c.710C>A	p.Ser237Tyr	missense_variant	8/9		XP_016884761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOOL	ENST00000373173.7	c.710C>A	p.Ser237Tyr	missense_variant	8/9	1	NM_198450.6	ENSP00000362268	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

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

May 26, 2022

The c.710C>A (p.S237Y) alteration is located in exon 8 (coding exon 8) of the APOOL gene. This alteration results from a C to A substitution at nucleotide position 710, causing the serine (S) at amino acid position 237 to be replaced by a tyrosine (Y). 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	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.80
DEOGEN2	Benign	0.21	T;.;T
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.86	D;D;D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.7	N;.;.
REVEL	Benign	0.071
Sift	Benign	0.048	D;.;.
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.31	B;.;.
Vest4		0.14
MutPred		0.20		Gain of solvent accessibility (P = 0.0081);.;Gain of solvent accessibility (P = 0.0081);
MVP		0.15
MPC		0.025
ClinPred		0.31	T
GERP RS		1.8
Varity_R		0.11
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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-84329389;