4-8504613-T-G

Position:

• chr4-8504613-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047449679.1(TRMT44):​c.2045-4185T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 152,064 control chromosomes in the GnomAD database, including 34,924 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 0.67 (34924 hom., cov: 32)
• Consequence: TRMT44 XM_047449679.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

Genes affected

TRMT44 (HGNC:26653): (tRNA methyltransferase 44 homolog) The protein encoded by this gene is a putative tRNA methyltransferase found in the cytoplasm. Defects in this gene may be a cause of partial epilepsy with pericentral spikes (PEPS), but that has not been proven definitively. [provided by RefSeq, May 2012]

ENSG00000205959 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRMT44	XM_047449679.1	c.2045-4185T>G		intron_variant			XP_047305635.1
TRMT44	XM_047449680.1	c.2045-4185T>G		intron_variant			XP_047305636.1
TRMT44	XM_047449681.1	c.2045-4185T>G		intron_variant			XP_047305637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000205959	ENST00000528132.1	n.171-4185T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101111 AN: 151946 Hom.: 34872 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.661

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.652

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.666 AC: 101228 AN: 152064 Hom.: 34924 Cov.: 32 AF XY: 0.665 AC XY: 49424 AN XY: 74332

Gnomad4 AFR AF: 0.866

Gnomad4 AMR AF: 0.662

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.524

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.650

Alfa AF: 0.595 Hom.: 12628

Bravo AF: 0.683

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2631723; hg19: chr4-8506340;