rs4929923

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 53 publications found

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

Our verdict: Benign. The variant received -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	ENST00000646038.2	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

African (AFR) AF: 0.530 AC: 3831 AN: 7234

American (AMR) AF: 0.566 AC: 5077 AN: 8964

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 4937 AN: 8024

East Asian (EAS) AF: 0.370 AC: 7125 AN: 19282

South Asian (SAS) AF: 0.537 AC: 4534 AN: 8446

European-Finnish (FIN) AF: 0.648 AC: 9899 AN: 15274

Middle Eastern (MID) AF: 0.565 AC: 627 AN: 1110

European-Non Finnish (NFE) AF: 0.626 AC: 90608 AN: 144842

Other (OTH) AF: 0.593 AC: 8511 AN: 14346

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

African (AFR) AF: 0.544 AC: 22567 AN: 41466

American (AMR) AF: 0.561 AC: 8580 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2163 AN: 3466

East Asian (EAS) AF: 0.403 AC: 2085 AN: 5180

South Asian (SAS) AF: 0.535 AC: 2580 AN: 4824

European-Finnish (FIN) AF: 0.650 AC: 6885 AN: 10598

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43162 AN: 67984

Other (OTH) AF: 0.587 AC: 1240 AN: 2114

Alfa AF: 0.612 Hom.: 113695

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
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4929923; hg19: chr11-8639200; COSMIC: COSV105167409; COSMIC: COSV105167409;