3-195571307-G-T

Variant names:

• chr3-195571307-G-T
• rs146246326
• NM_001647.4:c.304C>A

Variant summary

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

The NM_001647.4(APOD):​c.304C>A​(p.Pro102Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: APOD NM_001647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40

Genes affected

APOD (HGNC:612): (apolipoprotein D) This gene encodes a component of high density lipoprotein that has no marked similarity to other apolipoprotein sequences. It has a high degree of homology to plasma retinol-binding protein and other members of the alpha 2 microglobulin protein superfamily of carrier proteins, also known as lipocalins. This glycoprotein is closely associated with the enzyme lecithin:cholesterol acyltransferase - an enzyme involved in lipoprotein metabolism. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOD	NM_001647.4	c.304C>A	p.Pro102Thr	missense_variant	Exon 4 of 5	ENST00000343267.8	NP_001638.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOD	ENST00000343267.8	c.304C>A	p.Pro102Thr	missense_variant	Exon 4 of 5	1	NM_001647.4	ENSP00000345179.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251488 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135918

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10 AN XY: 727238

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: 0.0000108

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-6.9	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.034	D;.;.
Polyphen		0.91	P;.;.
Vest4		0.68
MutPred		0.42		Gain of sheet (P = 0.0477);.;Gain of sheet (P = 0.0477);
MVP		0.55
MPC		0.45
ClinPred		0.95	D
GERP RS		4.4
Varity_R		0.81
gMVP		0.58

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: rs146246326; hg19: chr3-195298178;