6-30210510-C-T

Variant names:

• chr6-30210510-C-T
• rs3132671
• NM_003449.5:c.-376+2795G>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.-376+2795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,988 control chromosomes in the GnomAD database, including 13,725 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 0.42 (13725 hom., cov: 31)
• Consequence: TRIM26 NM_003449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.36
• Publications: 30 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 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.-376+2795G>A		intron	N/A	NP_003440.1	Q12899
	TRIM26	NM_001242783.2		c.-155+2795G>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.-376+2795G>A		intron	N/A	ENSP00000410446.2	Q12899
	TRIM26	ENST00000453195.5	TSL:1	c.-155+2795G>A		intron	N/A	ENSP00000391879.1	Q12899
	TRIM26	ENST00000861717.1		c.-250+2795G>A		intron	N/A	ENSP00000531776.1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64117 AN: 151870 Hom.: 13697 Cov.: 31

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.422 AC: 64200 AN: 151988 Hom.: 13725 Cov.: 31 AF XY: 0.419 AC XY: 31130 AN XY: 74284

African (AFR) AF: 0.408 AC: 16923 AN: 41448

American (AMR) AF: 0.411 AC: 6271 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1604 AN: 5172

South Asian (SAS) AF: 0.398 AC: 1915 AN: 4812

European-Finnish (FIN) AF: 0.415 AC: 4389 AN: 10566

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30461 AN: 67944

Other (OTH) AF: 0.389 AC: 820 AN: 2110

Alfa AF: 0.436 Hom.: 52706

Bravo AF: 0.420

Asia WGS AF: 0.375 AC: 1304 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.084
DANN	Benign	0.45
PhyloP100		-2.4
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: rs3132671; hg19: chr6-30178287;