rs7629889

Positions:

• chr3-3145959-G-A

Variant summary

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

The NM_182916.3(TRNT1):​c.609-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 151,250 control chromosomes in the GnomAD database, including 1,569 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 0.14 (1569 hom., cov: 30)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

TRNT1 (HGNC:17341): (tRNA nucleotidyl transferase 1) The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

CRBN (HGNC:30185): (cereblon) This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRNT1	NM_182916.3	c.609-471G>A		intron_variant		ENST00000251607.11	NP_886552.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRNT1	ENST00000251607.11	c.609-471G>A		intron_variant		1	NM_182916.3	ENSP00000251607	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21369 AN: 151132 Hom.: 1564 Cov.: 30

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0571

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.137

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

GnomAD4 genome AF: 0.142 AC: 21402 AN: 151250 Hom.: 1569 Cov.: 30 AF XY: 0.142 AC XY: 10483 AN XY: 73812

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0572

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.135

Alfa AF: 0.146 Hom.: 879

Bravo AF: 0.148

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.85

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: rs7629889; hg19: chr3-3187643;