NM_182916.3:c.-27-20C>G

Variant names:

• chr3-3128994-C-G
• rs146036551
• NM_182916.3:c.-27-20C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182916.3(TRNT1):​c.-27-20C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,526,844 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (3 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (1 hom.)
• Consequence: TRNT1 NM_182916.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34
• 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: Laboratory for Molecular Medicine, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa and erythrocytic microcytosis

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-3128994-C-G is Benign according to our data. Variant chr3-3128994-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 381864.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00299 (456/152326) while in subpopulation AFR AF = 0.0104 (433/41560). AF 95% confidence interval is 0.00961. There are 3 homozygotes in GnomAd4. There are 218 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182916.3. 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.-27-20C>G		intron	N/A	NP_886552.3	Q96Q11-1
	TRNT1	NM_001367321.1		c.-27-20C>G		intron	N/A	NP_001354250.1	Q96Q11-1
	TRNT1	NM_001367322.1		c.-27-20C>G		intron	N/A	NP_001354251.1	Q96Q11-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNT1	ENST00000251607.11	TSL:1 MANE Select	c.-27-20C>G		intron	N/A	ENSP00000251607.6	Q96Q11-1
	TRNT1	ENST00000280591.10	TSL:1	c.-27-20C>G		intron	N/A	ENSP00000280591.6	Q96Q11-2
	TRNT1	ENST00000339437.11	TSL:1	c.-27-20C>G		intron	N/A	ENSP00000342985.6	Q96Q11-3

Frequencies

GnomAD3 genomes AF: 0.00300 AC: 456 AN: 152208 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000729 AC: 162 AN: 222142 AF XY: 0.000549

Gnomad AFR exome AF: 0.00910

Gnomad AMR exome AF: 0.000447

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000289

Gnomad OTH exome AF: 0.000576

GnomAD4 exome AF: 0.000293 AC: 403 AN: 1374518 Hom.: 1 Cov.: 24 AF XY: 0.000239 AC XY: 162 AN XY: 678986

African (AFR) AF: 0.0105 AC: 333 AN: 31598

American (AMR) AF: 0.000495 AC: 18 AN: 36330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22620

East Asian (EAS) AF: 0.00 AC: 0 AN: 38626

South Asian (SAS) AF: 0.0000135 AC: 1 AN: 74256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50668

Middle Eastern (MID) AF: 0.000372 AC: 2 AN: 5374

European-Non Finnish (NFE) AF: 0.00000567 AC: 6 AN: 1058498

Other (OTH) AF: 0.000760 AC: 43 AN: 56548

GnomAD4 genome AF: 0.00299 AC: 456 AN: 152326 Hom.: 3 Cov.: 33 AF XY: 0.00293 AC XY: 218 AN XY: 74480

African (AFR) AF: 0.0104 AC: 433 AN: 41560

American (AMR) AF: 0.00105 AC: 16 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2114

Alfa AF: 0.00132 Hom.: 0

Bravo AF: 0.00345

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.29
DANN	Benign	0.68
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs146036551; hg19: chr3-3170678;