rs3850699

Positions:

• chr10-102654464-A-G

Variant summary

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

The NM_030912.3(TRIM8):​c.571-189A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 582,090 control chromosomes in the GnomAD database, including 25,270 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 0.31 (7792 hom., cov: 32)
  • Exomes 𝑓: 0.27 (17478 hom.)
• Consequence: TRIM8 NM_030912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.996

Genes affected

TRIM8 (HGNC:15579): (tripartite motif containing 8) This gene encodes a member of the tripartite motif (TRIM) protein family. Based on similarities to other proteins, the encoded protein is suspected to be an E3 ubiquitin-protein ligase. Regulation of this gene may be altered in some cancers. Mutations resulting in a truncated protein product have been observed in early-onset epileptic encephalopathy (EOEE). [provided by RefSeq, Sep 2016]

LOC105378460 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM8	NM_030912.3	c.571-189A>G		intron_variant		ENST00000643721.2	NP_112174.2
LOC105378460	XR_007062272.1	n.85+583T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM8	ENST00000643721.2	c.571-189A>G		intron_variant			NM_030912.3	ENSP00000496301	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47332 AN: 151942 Hom.: 7791 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.273 AC: 117611 AN: 430028 Hom.: 17478 Cov.: 3 AF XY: 0.269 AC XY: 60958 AN XY: 226898

Gnomad4 AFR exome AF: 0.382

Gnomad4 AMR exome AF: 0.215

Gnomad4 ASJ exome AF: 0.290

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.332

Gnomad4 NFE exome AF: 0.299

Gnomad4 OTH exome AF: 0.288

GnomAD4 genome AF: 0.311 AC: 47337 AN: 152062 Hom.: 7792 Cov.: 32 AF XY: 0.307 AC XY: 22839 AN XY: 74332

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.329

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.293

Alfa AF: 0.297 Hom.: 13843

Bravo AF: 0.309

Asia WGS AF: 0.160 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.60
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3850699; hg19: chr10-104414221;