4-164972334-C-T

Position:

• chr4-164972334-C-T

Variant summary

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

The NM_001012414.3(TRIM61):​c.-337-1995G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,096 control chromosomes in the GnomAD database, including 24,892 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 0.56 (24892 hom., cov: 33)
• Consequence: TRIM61 NM_001012414.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613

Genes affected

TRIM61 (HGNC:24339): (tripartite motif containing 61) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM61	NM_001414904.1	c.-337-1995G>A		intron_variant		ENST00000710271.1	NP_001401833.1
TRIM61	NM_001012414.3	c.-337-1995G>A		intron_variant			NP_001012414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM61	ENST00000710271.1	c.-337-1995G>A		intron_variant			NM_001414904.1	ENSP00000518164	P1
TRIM61	ENST00000329314.6	c.-337-1995G>A		intron_variant		1		ENSP00000332288
TRIM61	ENST00000508856.2	c.-337-1995G>A		intron_variant				ENSP00000498736	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84977 AN: 151978 Hom.: 24843 Cov.: 33

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.572

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 85087 AN: 152096 Hom.: 24892 Cov.: 33 AF XY: 0.559 AC XY: 41525 AN XY: 74338

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.578

Alfa AF: 0.513 Hom.: 6070

Bravo AF: 0.582

Asia WGS AF: 0.726 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.28

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: rs10517825; hg19: chr4-165893486;