rs4929923

Variant names:

• chr11-8617653-T-C
• rs4929923
• NM_001388022.1:c.*291A>G

Variant summary

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

The NM_001388022.1(TRIM66):​c.*291A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 379,642 control chromosomes in the GnomAD database, including 68,232 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 0.59 (26947 hom., cov: 33)
  • Exomes 𝑓: 0.59 (41285 hom.)
• Consequence: TRIM66 NM_001388022.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599

Genes affected

TRIM66 (HGNC:29005): (tripartite motif containing 66) Predicted to enable chromatin binding activity and identical protein binding activity. Predicted to act upstream of or within negative regulation of transcription, DNA-templated. Located in aggresome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM66	NM_001388022.1	c.*291A>G		3_prime_UTR_variant	Exon 25 of 25	ENST00000646038.2	NP_001374951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM66	ENST00000646038	c.*291A>G		3_prime_UTR_variant	Exon 25 of 25		NM_001388022.1	ENSP00000495413.1

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89983 AN: 152002 Hom.: 26919 Cov.: 33

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.584

GnomAD4 exome AF: 0.594 AC: 135149 AN: 227522 Hom.: 41285 Cov.: 2 AF XY: 0.594 AC XY: 69216 AN XY: 116502

Gnomad4 AFR exome AF: 0.530

Gnomad4 AMR exome AF: 0.566

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.648

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.592 AC: 90055 AN: 152120 Hom.: 26947 Cov.: 33 AF XY: 0.590 AC XY: 43904 AN XY: 74362

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.635

Gnomad4 OTH AF: 0.587

Alfa AF: 0.616 Hom.: 53409

Bravo AF: 0.584

Asia WGS AF: 0.483 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	10
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4929923; hg19: chr11-8639200; COSMIC: COSV105167409; COSMIC: COSV105167409;