1-247857254-G-A

Variant names:

• chr1-247857254-G-A
• rs11204523
• NM_015431.4:c.8G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015431.4(TRIM58):​c.8G>A​(p.Trp3*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM58 NM_015431.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819
• Publications: 22 publications found

Genes affected

TRIM58 (HGNC:24150): (tripartite motif containing 58) Predicted to enable dynein heavy chain binding activity; dynein intermediate chain binding activity; and ubiquitin protein ligase activity. Predicted to be involved in several processes, including positive regulation of erythrocyte enucleation; protein ubiquitination; and regulation of nuclear migration along microtubule. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015431.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM58	NM_015431.4	MANE Select	c.8G>A	p.Trp3*	stop_gained	Exon 1 of 6	NP_056246.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM58	ENST00000366481.4	TSL:1 MANE Select	c.8G>A	p.Trp3*	stop_gained	Exon 1 of 6	ENSP00000355437.3

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1171188 Hom.: 0 Cov.: 67 AF XY: 0.00 AC XY: 0 AN XY: 562808

African (AFR) AF: 0.00 AC: 0 AN: 24118

American (AMR) AF: 0.00 AC: 0 AN: 10370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15724

East Asian (EAS) AF: 0.00 AC: 0 AN: 27156

South Asian (SAS) AF: 0.00 AC: 0 AN: 41214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3680

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 960954

Other (OTH) AF: 0.00 AC: 0 AN: 47062

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	35
DANN	Uncertain	0.99
Eigen	Benign	0.087
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.30	N
PhyloP100		0.82
Vest4		0.073
GERP RS		3.0
PromoterAI		0.20	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=110/90	disease causing (fs/PTC)

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: rs11204523; hg19: chr1-248020556;