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1-39841912-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_StrongBP6_ModerateBP7BS1BS2

The NM_017646.6(TRIT1):c.1236G>A(p.Ala412=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,604,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

TRIT1
NM_017646.6 splice_region, synonymous

Scores

2
Splicing: ADA: 0.0003078
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.693
Variant links:
Genes affected
TRIT1 (HGNC:20286): (tRNA isopentenyltransferase 1) This gene encodes a protein that that is targeted to the mitochondrion and modifies transfer RNAs (tRNAs) by adding a dimethylallyl group onto the adenine at position 37. This modification is important for maintaining the correct reading frame during protein translation. This gene is considered a tumor suppressor and its expression can decrease cell growth. Alternative splicing results in multiple transcripts variants, most of which are likely non-functional. [provided by RefSeq, Aug 2015]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-39841912-C-T is Benign according to our data. Variant chr1-39841912-C-T is described in ClinVar as [Benign]. Clinvar id is 2051052.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.693 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000146 (212/1452882) while in subpopulation AMR AF= 0.00377 (160/42466). AF 95% confidence interval is 0.00329. There are 1 homozygotes in gnomad4_exome. There are 91 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRIT1NM_017646.6 linkuse as main transcriptc.1236G>A p.Ala412= splice_region_variant, synonymous_variant 11/11 ENST00000316891.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIT1ENST00000316891.10 linkuse as main transcriptc.1236G>A p.Ala412= splice_region_variant, synonymous_variant 11/111 NM_017646.6 P1Q9H3H1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000987
AC:
15
AN:
151978
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000726
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000946
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.000658
AC:
158
AN:
240300
Hom.:
2
AF XY:
0.000500
AC XY:
65
AN XY:
129918
show subpopulations
Gnomad AFR exome
AF:
0.0000621
Gnomad AMR exome
AF:
0.00474
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0000353
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.000146
AC:
212
AN:
1452882
Hom.:
1
Cov.:
31
AF XY:
0.000126
AC XY:
91
AN XY:
722478
show subpopulations
Gnomad4 AFR exome
AF:
0.000182
Gnomad4 AMR exome
AF:
0.00377
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000238
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000325
Gnomad4 OTH exome
AF:
0.0000833
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000987
AC:
15
AN:
151978
Hom.:
0
Cov.:
32
AF XY:
0.0000674
AC XY:
5
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.0000726
Gnomad4 AMR
AF:
0.000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000946
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000480
Alfa
AF:
0.0000649
Hom.:
0
Bravo
AF:
0.000189

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
6.6
Dann
Benign
0.52
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00031
dbscSNV1_RF
Benign
0.0060
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201731718; hg19: chr1-40307584; COSMIC: COSV57549056; COSMIC: COSV57549056; API