14-50996604-A-G

Position:

• chr14-50996604-A-G

Variant summary

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

The ENST00000360392.4(TRIM9):​c.*1396T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 985,358 control chromosomes in the GnomAD database, including 1,341 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 0.073 (643 hom., cov: 33)
  • Exomes 𝑓: 0.034 (698 hom.)
• Consequence: TRIM9 ENST00000360392.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

Genes affected

TRIM9 (HGNC:16288): (tripartite motif containing 9) 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 cytoplasmic bodies. Its function has not been identified. Alternate splicing of this gene generates two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM9	NM_001387360.1	c.1603+1446T>C		intron_variant		ENST00000684578.1	NP_001374289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM9	ENST00000360392.4	c.*1396T>C		3_prime_UTR_variant	7/7	1		ENSP00000353561
TRIM9	ENST00000684578.1	c.1603+1446T>C		intron_variant			NM_001387360.1	ENSP00000507131
TRIM9	ENST00000298355.7	c.1603+1446T>C		intron_variant		1		ENSP00000298355	P1
TRIM9	ENST00000338969.9	c.1591+1446T>C		intron_variant		2		ENSP00000342970

Frequencies

GnomAD3 genomes AF: 0.0733 AC: 11156 AN: 152134 Hom.: 644 Cov.: 33

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.0848

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0641

GnomAD4 exome AF: 0.0341 AC: 28409 AN: 833106 Hom.: 698 Cov.: 30 AF XY: 0.0338 AC XY: 13006 AN XY: 384716

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0467

Gnomad4 ASJ exome AF: 0.0144

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.0822

Gnomad4 FIN exome AF: 0.0507

Gnomad4 NFE exome AF: 0.0296

Gnomad4 OTH exome AF: 0.0462

GnomAD4 genome AF: 0.0733 AC: 11166 AN: 152252 Hom.: 643 Cov.: 33 AF XY: 0.0759 AC XY: 5654 AN XY: 74452

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0529

Gnomad4 ASJ AF: 0.0150

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0292

Gnomad4 OTH AF: 0.0644

Alfa AF: 0.0394 Hom.: 201

Bravo AF: 0.0754

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.70

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: rs10483607; hg19: chr14-51463322;