5-34007604-A-C

Position:

• chr5-34007604-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014324.6(AMACR):​c.247+169T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,086 control chromosomes in the GnomAD database, including 6,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (6335 hom., cov: 32)
• Consequence: AMACR NM_014324.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-34007604-A-C is Benign according to our data. Variant chr5-34007604-A-C is described in ClinVar as [Benign]. Clinvar id is 1268751.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMACR	NM_014324.6	c.247+169T>G		intron_variant		ENST00000335606.11
C1QTNF3-AMACR	NR_037951.1	n.765-1705T>G		intron_variant, non_coding_transcript_variant
AMACR	NM_001167595.2	c.247+169T>G		intron_variant
AMACR	NM_203382.3	c.247+169T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMACR	ENST00000335606.11	c.247+169T>G		intron_variant		1	NM_014324.6	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38686 AN: 151968 Hom.: 6305 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38752 AN: 152086 Hom.: 6335 Cov.: 32 AF XY: 0.252 AC XY: 18757 AN XY: 74354

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.237

Alfa AF: 0.194 Hom.: 1952

Bravo AF: 0.265

Asia WGS AF: 0.193 AC: 673 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.30

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

Other links and lift over

dbSNP: rs34689; hg19: chr5-34007709;