rs6905949

Variant names:

• chr6-30172748-T-C
• rs6905949
• NM_033229.3:c.*399T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033229.3(TRIM15):​c.*399T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 346,774 control chromosomes in the GnomAD database, including 6,393 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 0.17 (2562 hom., cov: 33)
  • Exomes 𝑓: 0.18 (3831 hom.)
• Consequence: TRIM15 NM_033229.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.151
• Publications: 22 publications found

Genes affected

TRIM15 (HGNC:16284): (tripartite motif containing 15) 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 the cytoplasm. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033229.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM15	NM_033229.3	MANE Select	c.*399T>C		downstream_gene	N/A	NP_150232.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM15	ENST00000376694.9	TSL:1 MANE Select	c.*399T>C		downstream_gene	N/A	ENSP00000365884.4
	TRIM15	ENST00000619857.4	TSL:5	c.*399T>C		downstream_gene	N/A	ENSP00000484001.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26618 AN: 152152 Hom.: 2553 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.0776

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.183 AC: 35646 AN: 194504 Hom.: 3831 AF XY: 0.195 AC XY: 20321 AN XY: 104456

African (AFR) AF: 0.175 AC: 947 AN: 5422

American (AMR) AF: 0.129 AC: 1584 AN: 12246

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1732 AN: 5338

East Asian (EAS) AF: 0.223 AC: 1856 AN: 8334

South Asian (SAS) AF: 0.271 AC: 9375 AN: 34624

European-Finnish (FIN) AF: 0.0897 AC: 792 AN: 8828

Middle Eastern (MID) AF: 0.250 AC: 184 AN: 736

European-Non Finnish (NFE) AF: 0.160 AC: 17450 AN: 109204

Other (OTH) AF: 0.177 AC: 1726 AN: 9772

GnomAD4 genome AF: 0.175 AC: 26640 AN: 152270 Hom.: 2562 Cov.: 33 AF XY: 0.175 AC XY: 13012 AN XY: 74462

African (AFR) AF: 0.180 AC: 7493 AN: 41544

American (AMR) AF: 0.166 AC: 2538 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1219 AN: 3472

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5184

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4826

European-Finnish (FIN) AF: 0.0776 AC: 824 AN: 10620

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11411 AN: 68000

Other (OTH) AF: 0.210 AC: 443 AN: 2112

Alfa AF: 0.176 Hom.: 8907

Bravo AF: 0.182

Asia WGS AF: 0.210 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		-0.15

Splicing

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

Other links and lift over

dbSNP: rs6905949; hg19: chr6-30140525; COSMIC: COSV107480602;