9-37777623-C-A

Variant names:

• chr9-37777623-C-A
• rs200754365
• NM_144964.4:c.867C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_144964.4(TRMT10B):​c.867C>A​(p.Tyr289*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,613,866 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0024 (11 hom.)
• Consequence: TRMT10B NM_144964.4 stop_gained
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.43

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP6: Variant 9-37777623-C-A is Benign according to our data. Variant chr9-37777623-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 801362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10B	NM_144964.4	c.867C>A	p.Tyr289*	stop_gained	Exon 9 of 9	ENST00000297994.4	NP_659401.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT10B	ENST00000297994.4	c.867C>A	p.Tyr289*	stop_gained	Exon 9 of 9	1	NM_144964.4	ENSP00000297994.3
ENSG00000255872	ENST00000540557.1	n.*910+6291G>T		intron_variant	Intron 9 of 11	5		ENSP00000457548.1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 320 AN: 152072 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000604

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.00973

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00263

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00210 AC: 523 AN: 249550 AF XY: 0.00220

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000290

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00891

Gnomad NFE exome AF: 0.00238

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00240 AC: 3502 AN: 1461674 Hom.: 11 Cov.: 30 AF XY: 0.00239 AC XY: 1738 AN XY: 727154

Gnomad4 AFR exome AF: 0.000269 AC: 9 AN: 33476

Gnomad4 AMR exome AF: 0.000358 AC: 16 AN: 44724

Gnomad4 ASJ exome AF: 0.000115 AC: 3 AN: 26126

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39694

Gnomad4 SAS exome AF: 0.00121 AC: 104 AN: 86254

Gnomad4 FIN exome AF: 0.00800 AC: 427 AN: 53406

Gnomad4 NFE exome AF: 0.00251 AC: 2795 AN: 1111838

Gnomad4 Remaining exome AF: 0.00243 AC: 147 AN: 60388

GnomAD4 genome AF: 0.00210 AC: 320 AN: 152192 Hom.: 1 Cov.: 30 AF XY: 0.00247 AC XY: 184 AN XY: 74402

Gnomad4 AFR AF: 0.000602 AC: 0.000602265 AN: 0.000602265

Gnomad4 AMR AF: 0.000392 AC: 0.000392054 AN: 0.000392054

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000831 AC: 0.000830565 AN: 0.000830565

Gnomad4 FIN AF: 0.00973 AC: 0.00972616 AN: 0.00972616

Gnomad4 NFE AF: 0.00263 AC: 0.00263212 AN: 0.00263212

Gnomad4 OTH AF: 0.00142 AC: 0.00142315 AN: 0.00142315

Alfa AF: 0.00152 Hom.: 1

Bravo AF: 0.00135

ExAC AF: 0.00197 AC: 238

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00273

EpiControl AF: 0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EXOSC3: BS2; TRMT10B: BS2 -

May 28, 2019

Mendelics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Pathogenic	0.48
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.38
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.82	D
Vest4		0.18
GERP RS		3.7
Mutation Taster		=101/99	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

Publications

LitVar

Other links and lift over

dbSNP: rs200754365; hg19: chr9-37777620; COSMIC: COSV53050455; COSMIC: COSV53050455;