rs2278008

Variant names:

• chr5-33989413-C-G
• rs2278008
• NM_014324.6:c.829G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-33989413-C-G
• chr5-33989413-C-T

Variant summary

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

The NM_001167595.2(AMACR):​c.829G>C​(p.Glu277Gln) 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. 17/22 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. E277K) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AMACR NM_001167595.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• Publications: 53 publications found

Genes affected

AMACR (HGNC:451): (alpha-methylacyl-CoA racemase) This gene encodes a racemase. The encoded enzyme interconverts pristanoyl-CoA and C27-bile acylCoAs between their (R)- and (S)-stereoisomers. The conversion to the (S)-stereoisomers is necessary for degradation of these substrates by peroxisomal beta-oxidation. Encoded proteins from this locus localize to both mitochondria and peroxisomes. Mutations in this gene may be associated with adult-onset sensorimotor neuropathy, pigmentary retinopathy, and adrenomyeloneuropathy due to defects in bile acid synthesis. Alternatively spliced transcript variants have been described. Read-through transcription also exists between this gene and the upstream neighboring C1QTNF3 (C1q and tumor necrosis factor related protein 3) gene. [provided by RefSeq, Mar 2011]

C1QTNF3-AMACR (HGNC:49198): (C1QTNF3-AMACR readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring C1q and tumor necrosis factor related protein 3 (C1QTNF3) and alpha-methylacyl-CoA racemase (AMACR) genes on chromosome 5. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus not likely to produce a protein product. [provided by RefSeq, Mar 2011]

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=0.085235655).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167595.2. 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
	AMACR	NM_014324.6	MANE Select	c.829G>C	p.Glu277Gln	missense	Exon 5 of 5	NP_055139.4
	AMACR	NM_001167595.2		c.829G>C	p.Glu277Gln	missense	Exon 5 of 6	NP_001161067.1
	AMACR	NM_203382.3		c.*71G>C		3_prime_UTR	Exon 4 of 4	NP_976316.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMACR	ENST00000335606.11	TSL:1 MANE Select	c.829G>C	p.Glu277Gln	missense	Exon 5 of 5	ENSP00000334424.6
	AMACR	ENST00000382085.7	TSL:1	c.829G>C	p.Glu277Gln	missense	Exon 5 of 6	ENSP00000371517.3
	AMACR	ENST00000382072.6	TSL:1	c.*71G>C		3_prime_UTR	Exon 4 of 4	ENSP00000371504.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.12	N
PhyloP100		2.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.049
Sift	Benign	0.56	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.020
MutPred		0.34		Loss of stability (P = 0.0843)
MVP		0.48
MPC		0.055
ClinPred		0.46	T
GERP RS		5.7
Varity_R		0.051
gMVP		0.41
Mutation Taster		=98/2	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: rs2278008; hg19: chr5-33989518;