rs201731718

Variant names:

• chr1-39841912-C-A
• rs201731718
• NM_017646.6:c.1236G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-39841912-C-A
• chr1-39841912-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017646.6(TRIT1):​c.1236G>T​(p.Ala412Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A412A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIT1 NM_017646.6 splice_region, synonymous
• Scores: Splicing: ADA: 0.00001137
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=-0.693 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIT1	NM_017646.6	c.1236G>T	p.Ala412Ala	splice_region_variant, synonymous_variant	Exon 11 of 11	ENST00000316891.10	NP_060116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIT1	ENST00000316891.10	c.1236G>T	p.Ala412Ala	splice_region_variant, synonymous_variant	Exon 11 of 11	1	NM_017646.6	ENSP00000321810.5
TRIT1	ENST00000372818.5	c.1158G>T	p.Ala386Ala	splice_region_variant, synonymous_variant	Exon 10 of 10	1		ENSP00000361905.1
TRIT1	ENST00000462797.5	n.*76G>T		splice_region_variant, non_coding_transcript_exon_variant	Exon 10 of 10	5		ENSP00000473773.1
TRIT1	ENST00000462797.5	n.*76G>T		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000473773.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.0
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0060
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

Publications

LitVar

Other links and lift over

dbSNP: rs201731718; hg19: chr1-40307584;