5-33998668-G-A

Position:

chr5-33998668-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.712C>T(p.Pro238Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00445 in 1,612,120 control chromosomes in the GnomAD database, including 268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 144 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 124 hom. )

Consequence

AMACR
NM_014324.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 5.45

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]

AMACR links:

C1QTNF3-AMACR (HGNC:):

C1QTNF3-AMACR links:

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 (MetaRNN=0.0028857589).

BP6

Variant 5-33998668-G-A is Benign according to our data. Variant chr5-33998668-G-A is described in ClinVar as [Benign]. Clinvar id is 353254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AMACR	NM_014324.6 linkuse as main transcript	c.712C>T	p.Pro238Ser	missense_variant	4/5	ENST00000335606.11	NP_055139.4
C1QTNF3-AMACR	NR_037951.1 linkuse as main transcript	n.1068C>T		non_coding_transcript_exon_variant	8/9
AMACR	NM_001167595.2 linkuse as main transcript	c.712C>T	p.Pro238Ser	missense_variant	4/6		NP_001161067.1
AMACR	NM_203382.3 linkuse as main transcript	c.551C>T	p.Thr184Ile	missense_variant	3/4		NP_976316.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMACR	ENST00000335606.11 linkuse as main transcript	c.712C>T	p.Pro238Ser	missense_variant	4/5	1	NM_014324.6	ENSP00000334424	P1	Q9UHK6-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3615

AN:

151946

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0831

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00860

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0159

GnomAD3 exomes

AF:

0.00629

AC:

1578

AN:

250676

Hom.:

AF XY:

0.00474

AC XY:

642

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.0861

Gnomad AMR exome

AF:

0.00349

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00242

AC:

3539

AN:

1460056

Hom.:

124

Cov.:

AF XY:

0.00207

AC XY:

1501

AN XY:

726038

show subpopulations

Gnomad4 AFR exome

AF:

0.0849

Gnomad4 AMR exome

AF:

0.00419

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000123

Gnomad4 OTH exome

AF:

0.00519

GnomAD4 genome

AF:

0.0239

AC:

3637

AN:

152064

Hom.:

144

Cov.:

AF XY:

0.0229

AC XY:

1700

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0834

Gnomad4 AMR

AF:

0.00852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0157

Alfa

AF:

0.00549

Hom.:

Bravo

AF:

0.0279

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0790

AC:

348

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00786

AC:

954

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000328

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 16, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Alpha-methylacyl-CoA racemase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.;.;T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D;D

MetaRNN

Benign

0.0029

T;T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.2

M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-6.0

D;D;D;.;.

REVEL

Uncertain

0.31

Sift

Benign

0.056

T;D;T;.;.

Sift4G

Uncertain

0.046

D;D;D;D;D

Polyphen

0.83

P;.;P;.;.

Vest4

0.30

MVP

0.74

MPC

0.12

ClinPred

0.051

GERP RS

5.3

Varity_R

0.47

gMVP

0.78

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over