rs748212498

Variant names:

• chr6-31656036-C-A
• rs748212498
• NM_019101.3:c.70C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-31656036-C-A
• chr6-31656036-C-G
• chr6-31656036-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019101.3(APOM):​c.70C>A​(p.Pro24Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,437,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: APOM NM_019101.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• Publications: 0 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3558135).

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.70C>A	p.Pro24Thr	missense	Exon 1 of 6	NP_061974.2
	APOM	NM_001256169.2		c.-102-436C>A		intron	N/A	NP_001243098.1	O95445-2
	APOM	NR_045828.2		n.149-436C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOM	ENST00000375916.4	TSL:1 MANE Select	c.70C>A	p.Pro24Thr	missense	Exon 1 of 6	ENSP00000365081.3	O95445-1
	APOM	ENST00000375920.8	TSL:1	c.-102-436C>A		intron	N/A	ENSP00000365085.4	O95445-2
	APOM	ENST00000375918.6	TSL:2	c.-102-436C>A		intron	N/A	ENSP00000365083.2	Q5SRP5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1437518 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 712682

African (AFR) AF: 0.00 AC: 0 AN: 33146

American (AMR) AF: 0.0000243 AC: 1 AN: 41088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25718

East Asian (EAS) AF: 0.00 AC: 0 AN: 39034

South Asian (SAS) AF: 0.00 AC: 0 AN: 82694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099658

Other (OTH) AF: 0.0000336 AC: 2 AN: 59558

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.089
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.060
Sift	Benign	0.12	T
Sift4G	Benign	0.12	T
Polyphen		0.87	P
Vest4		0.30
MutPred		0.43		Loss of helix (P = 0.1299)
MVP		0.77
MPC		0.65
ClinPred		0.86	D
GERP RS		3.6
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.76
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs748212498; hg19: chr6-31623813;