rs16892150

Variant names:

• chr5-34005794-C-T
• rs16892150
• NM_014324.6:c.353G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-34005794-C-T
• chr5-34005794-C-A
• chr5-34005794-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014324.6(AMACR):​c.353G>A​(p.Arg118Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,614,058 control chromosomes in the GnomAD database, including 429 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R118W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.030 (218 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (211 hom.)
• Consequence: AMACR NM_014324.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.50
• Publications: 11 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]

ENSG00000289791 (HGNC:):

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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019286871).
• BP6: Variant 5-34005794-C-T is Benign according to our data. Variant chr5-34005794-C-T is described in ClinVar as Benign. ClinVar VariationId is 353255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014324.6. 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.353G>A	p.Arg118Gln	missense	Exon 2 of 5	NP_055139.4
	AMACR	NM_001167595.2		c.353G>A	p.Arg118Gln	missense	Exon 2 of 6	NP_001161067.1	Q9UHK6-5
	AMACR	NM_203382.3		c.353G>A	p.Arg118Gln	missense	Exon 2 of 4	NP_976316.1	Q9UHK6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMACR	ENST00000335606.11	TSL:1 MANE Select	c.353G>A	p.Arg118Gln	missense	Exon 2 of 5	ENSP00000334424.6	Q9UHK6-1
	AMACR	ENST00000382085.7	TSL:1	c.353G>A	p.Arg118Gln	missense	Exon 2 of 6	ENSP00000371517.3	Q9UHK6-5
	ENSG00000289791	ENST00000426255.6	TSL:2	c.353G>A	p.Arg118Gln	missense	Exon 2 of 5	ENSP00000476965.1	V9GYP4

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4494 AN: 152076 Hom.: 217 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0259

GnomAD2 exomes AF: 0.00781 AC: 1962 AN: 251340 AF XY: 0.00571

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.00431

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00309 AC: 4513 AN: 1461864 Hom.: 211 Cov.: 31 AF XY: 0.00266 AC XY: 1937 AN XY: 727232

African (AFR) AF: 0.109 AC: 3656 AN: 33480

American (AMR) AF: 0.00499 AC: 223 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.000158 AC: 176 AN: 1112012

Other (OTH) AF: 0.00695 AC: 420 AN: 60396

GnomAD4 genome AF: 0.0295 AC: 4497 AN: 152194 Hom.: 218 Cov.: 32 AF XY: 0.0279 AC XY: 2076 AN XY: 74420

African (AFR) AF: 0.103 AC: 4259 AN: 41494

American (AMR) AF: 0.0107 AC: 163 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.0256 AC: 54 AN: 2110

Alfa AF: 0.0103 Hom.: 185

Bravo AF: 0.0341

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0983 AC: 433

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00953 AC: 1157

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Alpha-methylacyl-CoA racemase deficiency (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.3
DANN	Benign	0.85
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	N
PhyloP100		-1.5
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.014
Sift	Benign	0.76	T
Sift4G	Benign	0.81	T
Polyphen		0.0020	B
Vest4		0.092
MVP		0.33
MPC		0.060
ClinPred		0.0017	T
GERP RS		-3.5
Varity_R		0.017
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs16892150; hg19: chr5-34005899;