6-30206354-C-T

Variant summary

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

The NM_003449.5(TRIM26):c.-375-1589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,142 control chromosomes in the GnomAD database, including 4,715 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 0.23 (4715 hom., cov: 33)
• Consequence: TRIM26 NM_003449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

Genes affected

TRIM26 (HGNC:12962): (tripartite motif containing 26) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Although the function of the protein is unknown, the RING domain suggests that the protein may have DNA-binding activity. The gene localizes to the major histocompatibility complex (MHC) class I region on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM26	NM_003449.5	c.-375-1589G>A		intron_variant		ENST00000454678.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM26	ENST00000454678.7	c.-375-1589G>A		intron_variant		1	NM_003449.5	P1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35471 AN: 152024 Hom.: 4692 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.234 AC: 35545 AN: 152142 Hom.: 4715 Cov.: 33 AF XY: 0.228 AC XY: 16949 AN XY: 74392

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.239

Alfa AF: 0.210 Hom.: 2052

Bravo AF: 0.244

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.2
Dann	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2021722; hg19: chr6-30174131;