NM_001647.4:c.178C>A

Variant names:

• chr3-195573917-G-T
• rs141030350
• NM_001647.4:c.178C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001647.4(APOD):​c.178C>A​(p.Arg60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. R60C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOD NM_001647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 5 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12483373).

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.178C>A	p.Arg60Ser	missense	Exon 3 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.178C>A	p.Arg60Ser	missense	Exon 3 of 5	ENSP00000345179.3	P05090
	APOD	ENST00000421243.5	TSL:3	c.262C>A	p.Arg88Ser	missense	Exon 4 of 6	ENSP00000415235.1	C9JF17
	APOD	ENST00000953531.1		c.244C>A	p.Arg82Ser	missense	Exon 4 of 6	ENSP00000623590.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.53	N
PhyloP100		1.3
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.12
Sift	Benign	0.76	T
Sift4G	Benign	0.78	T
Polyphen		0.010	B
Vest4		0.18
MutPred		0.45		Gain of sheet (P = 0.1451)
MVP		0.46
MPC		0.15
ClinPred		0.46	T
GERP RS		4.6
Varity_R		0.53
gMVP		0.31
Mutation Taster		=88/12	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: rs141030350; hg19: chr3-195300788;