6-31657231-T-G

Variant names:

• chr6-31657231-T-G
• rs34490746
• NM_019101.3:c.276T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019101.3(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. 15/22 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 NM_019101.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097839).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019101.3. 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
	APOM	NM_019101.3	MANE Select	c.276T>G	p.Asp92Glu	missense	Exon 3 of 6	NP_061974.2
	APOM	NM_001256169.2		c.60T>G	p.Asp20Glu	missense	Exon 3 of 6	NP_001243098.1	O95445-2
	APOM	NR_045828.2		n.317T>G		non_coding_transcript_exon	Exon 3 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOM	ENST00000375916.4	TSL:1 MANE Select	c.276T>G	p.Asp92Glu	missense	Exon 3 of 6	ENSP00000365081.3	O95445-1
	APOM	ENST00000375920.8	TSL:1	c.60T>G	p.Asp20Glu	missense	Exon 3 of 6	ENSP00000365085.4	O95445-2
	APOM	ENST00000375918.6	TSL:2	c.60T>G	p.Asp20Glu	missense	Exon 3 of 5	ENSP00000365083.2	Q5SRP5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.22
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.045
Sift	Benign	0.031	D
Sift4G	Uncertain	0.052	T
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
Mutation Taster		=93/7	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: rs34490746; hg19: chr6-31625008;