6-31657231-T-G

Position:

• chr6-31657231-T-G

Variant summary

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

The ENST00000375916.4(APOM):​c.276T>G​(p.Asp92Glu) 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. 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: APOM ENST00000375916.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

APOM (HGNC:13916): (apolipoprotein M) The protein encoded by this gene is an apolipoprotein and member of the lipocalin protein family. It is found associated with high density lipoproteins and to a lesser extent with low density lipoproteins and triglyceride-rich lipoproteins. The encoded protein is secreted through the plasma membrane but remains membrane-bound, where it is involved in lipid transport. Alternate splicing results in both coding and non-coding variants of this gene. [provided by RefSeq, Jan 2012]

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=0.097839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOM	NM_019101.3	c.276T>G	p.Asp92Glu	missense_variant	3/6	ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.60T>G	p.Asp20Glu	missense_variant	3/6		NP_001243098.1
APOM	XM_006715150.4	c.180T>G	p.Asp60Glu	missense_variant	3/6		XP_006715213.1
APOM	NR_045828.2	n.317T>G		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOM	ENST00000375916.4	c.276T>G	p.Asp92Glu	missense_variant	3/6	1	NM_019101.3	ENSP00000365081	P1
APOM	ENST00000375920.8	c.60T>G	p.Asp20Glu	missense_variant	3/6	1		ENSP00000365085
APOM	ENST00000375918.6	c.60T>G	p.Asp20Glu	missense_variant	3/5	2		ENSP00000365083

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T;.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.50	N
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;.;N
MutationTaster	Benign	0.84	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.045
Sift	Benign	0.031	D;D;D
Sift4G	Uncertain	0.052	T;D;D
Polyphen		0.0040	.;.;B
Vest4		0.15
MutPred		0.35		.;.;Loss of catalytic residue at K91 (P = 0.0769);
MVP		0.31
MPC		0.23
ClinPred		0.33	T
GERP RS		0.67
Varity_R		0.16
gMVP		0.31

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: rs34490746; hg19: chr6-31625008;