6-30208345-C-T

Variant names:

• chr6-30208345-C-T
• rs10947058
• NM_003449.5:c.-375-3580G>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.-375-3580G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 152,152 control chromosomes in the GnomAD database, including 444 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 0.064 (444 hom., cov: 32)
• Consequence: TRIM26 NM_003449.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390
• Publications: 10 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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.-375-3580G>A		intron	N/A	NP_003440.1	Q12899
	TRIM26	NM_001242783.2		c.-155+4960G>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.-375-3580G>A		intron	N/A	ENSP00000410446.2	Q12899
	TRIM26	ENST00000453195.5	TSL:1	c.-155+4960G>A		intron	N/A	ENSP00000391879.1	Q12899
	TRIM26	ENST00000861717.1		c.-249-3580G>A		intron	N/A	ENSP00000531776.1

Frequencies

GnomAD3 genomes AF: 0.0638 AC: 9693 AN: 152034 Hom.: 441 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0444

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0707

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

GnomAD4 genome AF: 0.0638 AC: 9712 AN: 152152 Hom.: 444 Cov.: 32 AF XY: 0.0627 AC XY: 4666 AN XY: 74382

African (AFR) AF: 0.107 AC: 4429 AN: 41494

American (AMR) AF: 0.0443 AC: 676 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3472

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5180

South Asian (SAS) AF: 0.0137 AC: 66 AN: 4816

European-Finnish (FIN) AF: 0.0550 AC: 582 AN: 10578

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0536 AC: 3644 AN: 68016

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0569 Hom.: 779

Bravo AF: 0.0654

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.6
DANN	Benign	0.85
PhyloP100		0.039
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: rs10947058; hg19: chr6-30176122;