Menu
GeneBe

5-33988023-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014324.6(AMACR):c.*1070C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 248,714 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 224 hom., cov: 33)
Exomes 𝑓: 0.024 ( 163 hom. )

Consequence

AMACR
NM_014324.6 3_prime_UTR

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.583
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 5-33988023-G-A is Benign according to our data. Variant chr5-33988023-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 353238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AMACRNM_014324.6 linkuse as main transcriptc.*1070C>T 3_prime_UTR_variant 5/5 ENST00000335606.11
C1QTNF3-AMACRNR_037951.1 linkuse as main transcriptn.2575C>T non_coding_transcript_exon_variant 9/9
AMACRNM_001167595.2 linkuse as main transcriptc.*285C>T 3_prime_UTR_variant 6/6
AMACRNM_203382.3 linkuse as main transcriptc.*1461C>T 3_prime_UTR_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AMACRENST00000335606.11 linkuse as main transcriptc.*1070C>T 3_prime_UTR_variant 5/51 NM_014324.6 P1Q9UHK6-1
AMACRENST00000382072.6 linkuse as main transcriptc.*1461C>T 3_prime_UTR_variant 4/41 Q9UHK6-4

Frequencies

GnomAD3 genomes
AF:
0.0355
AC:
5393
AN:
152096
Hom.:
223
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0749
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0446
Gnomad ASJ
AF:
0.00202
Gnomad EAS
AF:
0.166
Gnomad SAS
AF:
0.0523
Gnomad FIN
AF:
0.0171
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.00357
Gnomad OTH
AF:
0.0325
GnomAD4 exome
AF:
0.0240
AC:
2314
AN:
96500
Hom.:
163
Cov.:
0
AF XY:
0.0223
AC XY:
1090
AN XY:
48972
show subpopulations
Gnomad4 AFR exome
AF:
0.0717
Gnomad4 AMR exome
AF:
0.0482
Gnomad4 ASJ exome
AF:
0.00274
Gnomad4 EAS exome
AF:
0.162
Gnomad4 SAS exome
AF:
0.0514
Gnomad4 FIN exome
AF:
0.0125
Gnomad4 NFE exome
AF:
0.00344
Gnomad4 OTH exome
AF:
0.0287
GnomAD4 genome
AF:
0.0355
AC:
5408
AN:
152214
Hom.:
224
Cov.:
33
AF XY:
0.0375
AC XY:
2787
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.0749
Gnomad4 AMR
AF:
0.0449
Gnomad4 ASJ
AF:
0.00202
Gnomad4 EAS
AF:
0.165
Gnomad4 SAS
AF:
0.0519
Gnomad4 FIN
AF:
0.0171
Gnomad4 NFE
AF:
0.00357
Gnomad4 OTH
AF:
0.0350
Alfa
AF:
0.0224
Hom.:
25
Bravo
AF:
0.0397
Asia WGS
AF:
0.109
AC:
376
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Oculocutaneous albinism Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 24, 2019- -
Alpha-methylacyl-CoA racemase deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
4.5
Dann
Benign
0.72

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16892064; hg19: chr5-33988128; API