rs34490746

Positions:

• chr6-31657231-T-C
• chr6-31657231-T-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_019101.3(APOM):​c.276T>C​(p.Asp92=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00055 in 1,612,836 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0029 (6 hom., cov: 31)
  • Exomes 𝑓: 0.00030 (5 hom.)
• Consequence: APOM NM_019101.3 synonymous
• 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 Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-0.224 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOM	NM_019101.3	c.276T>C	p.Asp92=	synonymous_variant	3/6	ENST00000375916.4	NP_061974.2
APOM	NM_001256169.2	c.60T>C	p.Asp20=	synonymous_variant	3/6		NP_001243098.1
APOM	XM_006715150.4	c.180T>C	p.Asp60=	synonymous_variant	3/6		XP_006715213.1
APOM	NR_045828.2	n.317T>C		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>C	p.Asp92=	synonymous_variant	3/6	1	NM_019101.3	ENSP00000365081	P1
APOM	ENST00000375920.8	c.60T>C	p.Asp20=	synonymous_variant	3/6	1		ENSP00000365085
APOM	ENST00000375918.6	c.60T>C	p.Asp20=	synonymous_variant	3/5	2		ENSP00000365083

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 151990 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.00996

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.000649 AC: 160 AN: 246620 Hom.: 5 AF XY: 0.000394 AC XY: 53 AN XY: 134430

Gnomad AFR exome AF: 0.00801

Gnomad AMR exome AF: 0.000986

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000304 AC: 444 AN: 1460754 Hom.: 5 Cov.: 32 AF XY: 0.000231 AC XY: 168 AN XY: 726690

Gnomad4 AFR exome AF: 0.00959

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.00291 AC: 443 AN: 152082 Hom.: 6 Cov.: 31 AF XY: 0.00276 AC XY: 205 AN XY: 74334

Gnomad4 AFR AF: 0.00999

Gnomad4 AMR AF: 0.00151

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.000444 Hom.: 0

Bravo AF: 0.00340

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.8
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;