rs1491235

Variant names:

• chr4-99546722-A-G
• rs1491235
• NM_001134665.3:c.*2366T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001134665.3(TRMT10A):​c.*2366T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,904 control chromosomes in the GnomAD database, including 10,100 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10100 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TRMT10A NM_001134665.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• Publications: 6 publications found

Genes affected

TRMT10A (HGNC:28403): (tRNA methyltransferase 10A) This gene encodes a protein that belongs to the tRNA (Guanine-1)-methyltransferase family. A similar gene in yeast modifies several different tRNA species. Mutations in this gene are associated with microcephaly, short stature, and impaired glucose metabolism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

TRMT10A Gene-Disease associations (from GenCC):

• microcephaly, short stature, and impaired glucose metabolism 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• primary microcephaly-mild intellectual disability-young-onset diabetes syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRMT10A	NM_001134665.3	c.*2366T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000394876.7	NP_001128137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRMT10A	ENST00000394876.7	c.*2366T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_001134665.3	ENSP00000378342.2
TRMT10A	ENST00000394877.7	c.*2366T>C		3_prime_UTR_variant	Exon 8 of 8	2		ENSP00000378343.3
TRMT10A	ENST00000273962.7	c.*2366T>C		downstream_gene_variant		1		ENSP00000273962.3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53476 AN: 151786 Hom.: 10069 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.364

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.353 AC: 53547 AN: 151904 Hom.: 10100 Cov.: 32 AF XY: 0.349 AC XY: 25923 AN XY: 74240

African (AFR) AF: 0.487 AC: 20172 AN: 41426

American (AMR) AF: 0.302 AC: 4614 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3468

East Asian (EAS) AF: 0.335 AC: 1729 AN: 5168

South Asian (SAS) AF: 0.392 AC: 1889 AN: 4814

European-Finnish (FIN) AF: 0.207 AC: 2187 AN: 10552

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20030 AN: 67906

Other (OTH) AF: 0.370 AC: 782 AN: 2112

Alfa AF: 0.312 Hom.: 8557

Bravo AF: 0.360

Asia WGS AF: 0.402 AC: 1389 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.74
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs1491235; hg19: chr4-100467879;