rs114580856

Variant names:

• chr3-3127088-C-A
• rs114580856
• NM_182916.3:c.-28+98C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367322.1(TRNT1):​c.-229C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,430 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (91 hom., cov: 33)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: TRNT1 NM_001367322.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.48
• Publications: 0 publications found

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]

TRNT1 Gene-Disease associations (from GenCC):

• congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
• retinitis pigmentosa and erythrocytic microcytosis

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 3-3127088-C-A is Benign according to our data. Variant chr3-3127088-C-A is described in ClinVar as Benign. ClinVar VariationId is 1326595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367322.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNT1	NM_182916.3	MANE Select	c.-28+98C>A		intron	N/A	NP_886552.3	Q96Q11-1
	TRNT1	NM_001367322.1		c.-229C>A		5_prime_UTR	Exon 1 of 8	NP_001354251.1	Q96Q11-1
	TRNT1	NM_001367323.1		c.-958C>A		5_prime_UTR	Exon 1 of 8	NP_001354252.1	Q96Q11-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNT1	ENST00000251607.11	TSL:1 MANE Select	c.-28+98C>A		intron	N/A	ENSP00000251607.6	Q96Q11-1
	TRNT1	ENST00000280591.10	TSL:1	c.-28+98C>A		intron	N/A	ENSP00000280591.6	Q96Q11-2
	TRNT1	ENST00000339437.11	TSL:1	c.-28+98C>A		intron	N/A	ENSP00000342985.6	Q96Q11-3

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2976 AN: 152216 Hom.: 89 Cov.: 33

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0172

GnomAD4 exome AF: 0.0104 AC: 1 AN: 96 Hom.: 0 Cov.: 0 AF XY: 0.0156 AC XY: 1 AN XY: 64

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 80

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0196 AC: 2993 AN: 152334 Hom.: 91 Cov.: 33 AF XY: 0.0185 AC XY: 1376 AN XY: 74504

African (AFR) AF: 0.0675 AC: 2806 AN: 41576

American (AMR) AF: 0.00732 AC: 112 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68022

Other (OTH) AF: 0.0170 AC: 36 AN: 2116

Alfa AF: 0.0167 Hom.: 8

Bravo AF: 0.0219

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.93
DANN	Benign	0.63
PhyloP100		-2.5
PromoterAI		0.14	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs114580856; hg19: chr3-3168772;