1-247857271-C-G

Variant names:

• chr1-247857271-C-G
• rs758862161
• NM_015431.4:c.25C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015431.4(TRIM58):​c.25C>G​(p.Arg9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000835 in 1,197,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: TRIM58 NM_015431.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21346223).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM58	NM_015431.4	MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 6	NP_056246.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM58	ENST00000366481.4	TSL:1 MANE Select	c.25C>G	p.Arg9Gly	missense	Exon 1 of 6	ENSP00000355437.3	Q8NG06

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.35e-7 AC: 1 AN: 1197956 Hom.: 0 Cov.: 35 AF XY: 0.00000173 AC XY: 1 AN XY: 578012

African (AFR) AF: 0.00 AC: 0 AN: 24620

American (AMR) AF: 0.00 AC: 0 AN: 11706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16266

East Asian (EAS) AF: 0.00 AC: 0 AN: 27758

South Asian (SAS) AF: 0.00 AC: 0 AN: 46730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4014

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 975822

Other (OTH) AF: 0.00 AC: 0 AN: 48298

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.067
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.82	L
PhyloP100		0.41
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.14
Sift	Benign	0.090	T
Sift4G	Benign	0.11	T
Polyphen		0.95	P
Vest4		0.40
MutPred		0.33		Gain of catalytic residue at R9 (P = 0.1323)
MVP		0.60
MPC		1.6
ClinPred		0.46	T
GERP RS		2.5
PromoterAI		0.041	Neutral
Varity_R		0.19
gMVP		0.19
Mutation Taster		=83/17	polymorphism

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: rs758862161; hg19: chr1-248020573;