rs115768555

Variant names:

• chr9-37777651-T-C
• rs115768555
• NM_144964.4:c.895T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_144964.4(TRMT10B):​c.895T>C​(p.Leu299Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000703 in 1,614,076 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 30)
  • Exomes 𝑓: 0.00040 (2 hom.)
• Consequence: TRMT10B NM_144964.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.741
• Publications: 2 publications found

Genes affected

TRMT10B (HGNC:26454): (tRNA methyltransferase 10B) Enables tRNA (guanine-N1-)-methyltransferase activity. Predicted to be involved in mitochondrial tRNA processing. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000255872 (HGNC:):

EXOSC3 (HGNC:17944): (exosome component 3) This gene encodes a non-catalytic component of the human exosome, a complex with 3'-5' exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2012]

EXOSC3 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 1B

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina, Genomics England PanelApp, G2P
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 9-37777651-T-C is Benign according to our data. Variant chr9-37777651-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3387859.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.741 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144964.4. 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
	TRMT10B	NM_144964.4	MANE Select	c.895T>C	p.Leu299Leu	synonymous	Exon 9 of 9	NP_659401.2	Q6PF06-1
	TRMT10B	NM_001286950.2		c.715T>C	p.Leu239Leu	synonymous	Exon 8 of 8	NP_001273879.1	Q6PF06-5
	TRMT10B	NM_001286952.2		c.634T>C	p.Leu212Leu	synonymous	Exon 7 of 7	NP_001273881.1	Q6PF06-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRMT10B	ENST00000297994.4	TSL:1 MANE Select	c.895T>C	p.Leu299Leu	synonymous	Exon 9 of 9	ENSP00000297994.3	Q6PF06-1
	TRMT10B	ENST00000488673.6	TSL:1	n.*482T>C		non_coding_transcript_exon	Exon 9 of 9	ENSP00000437395.1	Q6PF06-3
	TRMT10B	ENST00000488673.6	TSL:1	n.*482T>C		3_prime_UTR	Exon 9 of 9	ENSP00000437395.1	Q6PF06-3

Frequencies

GnomAD3 genomes AF: 0.00360 AC: 547 AN: 152134 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000942 AC: 235 AN: 249556 AF XY: 0.000665

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.000319

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000400 AC: 584 AN: 1461824 Hom.: 2 Cov.: 30 AF XY: 0.000311 AC XY: 226 AN XY: 727214

African (AFR) AF: 0.0153 AC: 511 AN: 33470

American (AMR) AF: 0.000492 AC: 22 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111974

Other (OTH) AF: 0.000629 AC: 38 AN: 60396

GnomAD4 genome AF: 0.00361 AC: 550 AN: 152252 Hom.: 4 Cov.: 30 AF XY: 0.00329 AC XY: 245 AN XY: 74442

African (AFR) AF: 0.0128 AC: 531 AN: 41542

American (AMR) AF: 0.000654 AC: 10 AN: 15300

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00163 Hom.: 2

Bravo AF: 0.00441

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.1
DANN	Benign	0.84
PhyloP100		-0.74
Mutation Taster		=100/0	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: rs115768555; hg19: chr9-37777648;