rs116700990

Variant names:

• chr3-3126942-C-A
• rs116700990
• NM_182916.3:c.-76C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-3126942-C-A
• chr3-3126942-C-G
• chr3-3126942-C-T

Variant summary

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

The NM_182916.3(TRNT1):​c.-76C>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 0.0313 in 152,836 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (156 hom., cov: 33)
  • Exomes 𝑓: 0.014 (2 hom.)
• Consequence: TRNT1 NM_182916.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.64
• Publications: 3 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)

LOC124909339 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 3-3126942-C-A is Benign according to our data. Variant chr3-3126942-C-A is described in ClinVar as Benign. ClinVar VariationId is 1326594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0843 is higher than 0.05.

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.-76C>A		5_prime_UTR	Exon 1 of 8	NP_886552.3	Q96Q11-1
	TRNT1	NM_001367321.1		c.-76C>A		5_prime_UTR	Exon 1 of 9	NP_001354250.1	Q96Q11-1
	TRNT1	NM_001367322.1		c.-375C>A		5_prime_UTR	Exon 1 of 8	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.-76C>A		5_prime_UTR	Exon 1 of 8	ENSP00000251607.6	Q96Q11-1
	TRNT1	ENST00000339437.11	TSL:1	c.-76C>A		5_prime_UTR	Exon 1 of 3	ENSP00000342985.6	Q96Q11-3
	TRNT1	ENST00000866264.1		c.-76C>A		5_prime_UTR	Exon 1 of 9	ENSP00000536323.1

Frequencies

GnomAD3 genomes AF: 0.0312 AC: 4752 AN: 152226 Hom.: 154 Cov.: 33

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00165

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.0142 AC: 7 AN: 492 Hom.: 2 Cov.: 0 AF XY: 0.0137 AC XY: 5 AN XY: 366

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.00 AC: 0 AN: 30

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

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

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.00966 AC: 4 AN: 414

Other (OTH) AF: 0.100 AC: 2 AN: 20

GnomAD4 genome AF: 0.0313 AC: 4775 AN: 152344 Hom.: 156 Cov.: 33 AF XY: 0.0294 AC XY: 2191 AN XY: 74500

African (AFR) AF: 0.0866 AC: 3602 AN: 41578

American (AMR) AF: 0.0230 AC: 352 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4830

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10630

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0104 AC: 707 AN: 68030

Other (OTH) AF: 0.0312 AC: 66 AN: 2114

Alfa AF: 0.00340 Hom.: 0

Bravo AF: 0.0356

Asia WGS AF: 0.00549 AC: 19 AN: 3476

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	-0.68
CADD	Benign	2.5
DANN	Benign	0.88
PhyloP100		-2.6
PromoterAI		0.088	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: rs116700990; hg19: chr3-3168626;