1-117116737-T-C

Position:

• chr1-117116737-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025188.4(TRIM45):​c.1231A>G​(p.Arg411Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TRIM45 NM_025188.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0970

Genes affected

TRIM45 (HGNC:19018): (tripartite motif containing 45) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to act upstream of or within bone development. Located in cytosol; intercellular bridge; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM45 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM45	NM_025188.4	c.1231A>G	p.Arg411Gly	missense_variant	3/6	ENST00000256649.9	NP_079464.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM45	ENST00000256649.9	c.1231A>G	p.Arg411Gly	missense_variant	3/6	1	NM_025188.4	ENSP00000256649.4
TRIM45	ENST00000369464.7	c.1177A>G	p.Arg393Gly	missense_variant	3/6	1		ENSP00000358476.3
TRIM45	ENST00000369461.3	c.1060A>G	p.Arg354Gly	missense_variant	4/7	5		ENSP00000358473.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727206

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.1231A>G (p.R411G) alteration is located in exon 3 (coding exon 3) of the TRIM45 gene. This alteration results from a A to G substitution at nucleotide position 1231, causing the arginine (R) at amino acid position 411 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.0	L;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N;N;D
REVEL	Uncertain	0.39
Sift	Benign	0.031	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.95	P;D;.
Vest4		0.34
MutPred		0.62		Gain of catalytic residue at R411 (P = 0.0293);.;.;
MVP		0.96
MPC		0.33
ClinPred		0.55	D
GERP RS		2.7
Varity_R		0.18
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-117659359;