NM_003449.5:c.-375-1589G>A

Variant names:

• chr6-30206354-C-T
• rs2021722
• NM_003449.5:c.-375-1589G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 64 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003449.5. 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
	TRIM26	NM_003449.5	MANE Select	c.-375-1589G>A		intron	N/A	NP_003440.1	Q12899
	TRIM26	NM_001242783.2		c.-154-5216G>A		intron	N/A	NP_001229712.1	A0A024RCP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM26	ENST00000454678.7	TSL:1 MANE Select	c.-375-1589G>A		intron	N/A	ENSP00000410446.2	Q12899
	TRIM26	ENST00000453195.5	TSL:1	c.-154-5216G>A		intron	N/A	ENSP00000391879.1	Q12899
	TRIM26	ENST00000861717.1		c.-249-1589G>A		intron	N/A	ENSP00000531776.1

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

African (AFR) AF: 0.347 AC: 14386 AN: 41468

American (AMR) AF: 0.187 AC: 2867 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3470

East Asian (EAS) AF: 0.101 AC: 520 AN: 5166

South Asian (SAS) AF: 0.278 AC: 1343 AN: 4824

European-Finnish (FIN) AF: 0.101 AC: 1074 AN: 10608

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13869 AN: 67992

Other (OTH) AF: 0.239 AC: 505 AN: 2110

Alfa AF: 0.227 Hom.: 4113

Bravo AF: 0.244

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.55
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2021722; hg19: chr6-30174131;