3-195579377-G-C

Variant names:

• chr3-195579377-G-C
• rs183224694
• NM_001647.4:c.85C>G

Variant summary

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

The NM_001647.4(APOD):​c.85C>G​(p.Pro29Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOD NM_001647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.40
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001647.4. 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
	APOD	NM_001647.4	MANE Select	c.85C>G	p.Pro29Ala	missense	Exon 2 of 5	NP_001638.1	P05090

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOD	ENST00000343267.8	TSL:1 MANE Select	c.85C>G	p.Pro29Ala	missense	Exon 2 of 5	ENSP00000345179.3	P05090
	APOD	ENST00000421243.5	TSL:3	c.169C>G	p.Pro57Ala	missense	Exon 3 of 6	ENSP00000415235.1	C9JF17
	APOD	ENST00000953531.1		c.85C>G	p.Pro29Ala	missense	Exon 3 of 6	ENSP00000623590.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Uncertain	0.45	T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.4
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.24
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.017	D
Polyphen		0.92	P
Vest4		0.45
MutPred		0.53		Loss of ubiquitination at K27 (P = 0.0509)
MVP		0.69
MPC		0.43
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.58
gMVP		0.69
Mutation Taster		=74/26	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: rs183224694; hg19: chr3-195306248;