rs138415849

Variant names:

• chr1-39883476-C-A
• rs138415849
• NM_017646.6:c.16G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-39883476-C-A
• chr1-39883476-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017646.6(TRIT1):​c.16G>T​(p.Ala6Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,443,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A6T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIT1 NM_017646.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 4 publications found

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]

MYCL-AS1 (HGNC:40386): (MYCL antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16407797).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017646.6. 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
	TRIT1	NM_017646.6	MANE Select	c.16G>T	p.Ala6Ser	missense	Exon 1 of 11	NP_060116.2
	TRIT1	NM_001312691.1		c.16G>T	p.Ala6Ser	missense	Exon 1 of 10	NP_001299620.1	Q9H3H1-4
	TRIT1	NM_001312692.1		c.16G>T	p.Ala6Ser	missense	Exon 1 of 9	NP_001299621.1	Q9H3H1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIT1	ENST00000316891.10	TSL:1 MANE Select	c.16G>T	p.Ala6Ser	missense	Exon 1 of 11	ENSP00000321810.5	Q9H3H1-1
	TRIT1	ENST00000372818.5	TSL:1	c.16G>T	p.Ala6Ser	missense	Exon 1 of 10	ENSP00000361905.1	Q9H3H1-4
	TRIT1	ENST00000441669.6	TSL:1	c.16G>T	p.Ala6Ser	missense	Exon 1 of 9	ENSP00000388333.2	Q9H3H1-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000409 AC: 1 AN: 244576 AF XY: 0.00000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443758 Hom.: 0 Cov.: 32 AF XY: 0.00000280 AC XY: 2 AN XY: 714178

African (AFR) AF: 0.00 AC: 0 AN: 33068

American (AMR) AF: 0.0000226 AC: 1 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39036

South Asian (SAS) AF: 0.00 AC: 0 AN: 85806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53026

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5480

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097844

Other (OTH) AF: 0.00 AC: 0 AN: 59392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		4.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.090
Sift	Benign	0.15	T
Sift4G	Benign	0.31	T
Polyphen		0.037	B
Vest4		0.46
MutPred		0.16		Gain of disorder (P = 0.0357)
MVP		0.60
MPC		0.29
ClinPred		0.42	T
GERP RS		4.8
PromoterAI		-0.099	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.085
gMVP		0.41
Mutation Taster		=85/15	polymorphism

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: rs138415849; hg19: chr1-40349148;