rs9291

Variant names:

• chr14-100282507-A-C
• rs9291
• NM_003403.5:c.*4907A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003403.5(YY1):​c.*4907A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.894 in 152,156 control chromosomes in the GnomAD database, including 61,813 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.89 (61809 hom., cov: 31)
  • Exomes 𝑓: 1.0 (4 hom.)
• Consequence: YY1 NM_003403.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

Genes affected

YY1 (HGNC:12856): (YY1 transcription factor) YY1 is a ubiquitously distributed transcription factor belonging to the GLI-Kruppel class of zinc finger proteins. The protein is involved in repressing and activating a diverse number of promoters. YY1 may direct histone deacetylases and histone acetyltransferases to a promoter in order to activate or repress the promoter, thus implicating histone modification in the function of YY1. [provided by RefSeq, Jul 2008]

ENSG00000259052 (HGNC:):

SLC25A29 (HGNC:20116): (solute carrier family 25 member 29) This gene encodes a nuclear-encoded mitochondrial protein that is a member of the large family of solute carrier family 25 (SLC25) mitochondrial transporters. The members of this superfamily are involved in numerous metabolic pathways and cell functions. This gene product was previously reported to be a mitochondrial carnitine-acylcarnitine-like (CACL) translocase (PMID:128829710) or an ornithine transporter (designated ORNT3, PMID:19287344), however, a recent study characterized the main role of this protein as a mitochondrial transporter of basic amino acids, with a preference for arginine and lysine (PMID:24652292). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YY1	NM_003403.5	c.*4907A>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000262238.10	NP_003394.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YY1	ENST00000262238.10	c.*4907A>C		3_prime_UTR_variant	Exon 5 of 5	1	NM_003403.5	ENSP00000262238.4
ENSG00000259052	ENST00000553954.1	n.100-2442T>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.894 AC: 135912 AN: 152030 Hom.: 61765 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.964

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.971

Gnomad FIN AF: 0.968

Gnomad MID AF: 0.955

Gnomad NFE AF: 0.964

Gnomad OTH AF: 0.927

GnomAD4 exome AF: 1.00 AC: 8 AN: 8 Hom.: 4 Cov.: 0 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.894 AC: 136012 AN: 152148 Hom.: 61809 Cov.: 31 AF XY: 0.898 AC XY: 66845 AN XY: 74408

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.943

Gnomad4 ASJ AF: 0.964

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.972

Gnomad4 FIN AF: 0.968

Gnomad4 NFE AF: 0.964

Gnomad4 OTH AF: 0.927

Alfa AF: 0.946 Hom.: 68104

Bravo AF: 0.885

Asia WGS AF: 0.972 AC: 3382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.68

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: rs9291; hg19: chr14-100748844;