rs707922

Positions:

• chr6-31657730-G-A
• chr6-31657730-G-C
• chr6-31657730-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019101.3(APOM):​c.541+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: APOM NM_019101.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001500
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.862

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29703164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOM	NM_019101.3	c.541+7G>A		splice_region_variant, intron_variant		ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.325+7G>A		splice_region_variant, intron_variant			NP_001243098.1
APOM	XM_006715150.4	c.445+7G>A		splice_region_variant, intron_variant			XP_006715213.1
APOM	NR_045828.2	n.582+7G>A		splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOM	ENST00000375916.4	c.541+7G>A		splice_region_variant, intron_variant		1	NM_019101.3	ENSP00000365081	P1
APOM	ENST00000375920.8	c.325+7G>A		splice_region_variant, intron_variant		1		ENSP00000365085
APOM	ENST00000375918.6	c.332G>A	p.Gly111Glu	missense_variant	5/5	2		ENSP00000365083

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455000 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 724308

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.6
DANN	Benign	0.66
DEOGEN2	Benign	0.022	T
Eigen	Benign	0.18
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	1.8	N
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D
Vest4		0.12
MutPred		0.19		Loss of loop (P = 0.0112);
MVP		0.73
ClinPred		0.21	T
GERP RS		2.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0040
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: rs707922; hg19: chr6-31625507;