rs2306257

Positions:

• chr1-33165468-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018207.3(TRIM62):​c.504+3G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,593,538 control chromosomes in the GnomAD database, including 44,425 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 0.20 (3226 hom., cov: 32)
  • Exomes 𝑓: 0.24 (41199 hom.)
• Consequence: TRIM62 NM_018207.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.9927
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

Genes affected

TRIM62 (HGNC:25574): (tripartite motif containing 62) Enables identical protein binding activity; transcription coactivator activity; and ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of viral transcription; positive regulation of NF-kappaB transcription factor activity; and positive regulation of antifungal innate immune response. Is active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM62	NM_018207.3	c.504+3G>T		splice_donor_region_variant, intron_variant		ENST00000291416.10
AZIN2	XM_047443457.1	c.*4503C>A		3_prime_UTR_variant	10/10
TRIM62	NM_001330483.2	c.141+3G>T		splice_donor_region_variant, intron_variant
ZNF362	XM_047447108.1	c.-24+37019C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM62	ENST00000291416.10	c.504+3G>T		splice_donor_region_variant, intron_variant		1	NM_018207.3	P1
	ENST00000624339.1	n.2618C>A		non_coding_transcript_exon_variant	1/1
TRIM62	ENST00000543586.1	c.141+3G>T		splice_donor_region_variant, intron_variant		2
TRIM62	ENST00000485148.1	n.553+3G>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29806 AN: 152120 Hom.: 3229 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.228 AC: 50973 AN: 223550 Hom.: 6139 AF XY: 0.236 AC XY: 28561 AN XY: 120914

Gnomad AFR exome AF: 0.0876

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.215

Gnomad SAS exome AF: 0.309

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.238

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.236 AC: 340164 AN: 1441300 Hom.: 41199 Cov.: 32 AF XY: 0.239 AC XY: 170793 AN XY: 715510

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.310

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.196 AC: 29810 AN: 152238 Hom.: 3226 Cov.: 32 AF XY: 0.199 AC XY: 14816 AN XY: 74418

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.215

Alfa AF: 0.225 Hom.: 5176

Bravo AF: 0.184

Asia WGS AF: 0.208 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.81
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: rs2306257; hg19: chr1-33631069; COSMIC: COSV52222527;