8-125430912-G-C

Variant names:

• chr8-125430912-G-C
• NM_025195.4:c.10G>C

Variant summary

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

The NM_025195.4(TRIB1):​c.10G>C​(p.Gly4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: TRIB1 NM_025195.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91
• Publications: 0 publications found

Genes affected

TRIB1 (HGNC:16891): (tribbles pseudokinase 1) Enables mitogen-activated protein kinase kinase binding activity and protein kinase inhibitor activity. Involved in several processes, including JNK cascade; negative regulation of lipopolysaccharide-mediated signaling pathway; and regulation of protein kinase activity. Located in cytoplasm and nucleus. [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=0.21294805).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025195.4. 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
	TRIB1	NM_025195.4	MANE Select	c.10G>C	p.Gly4Arg	missense	Exon 1 of 3	NP_079471.1	Q96RU8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIB1	ENST00000311922.4	TSL:1 MANE Select	c.10G>C	p.Gly4Arg	missense	Exon 1 of 3	ENSP00000312150.3	Q96RU8-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.69	N
PhyloP100		1.9
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.042
Sift	Uncertain	0.026	D
Sift4G	Benign	0.11	T
Polyphen		0.80	P
Vest4		0.26
MutPred		0.29		Gain of methylation at G4 (P = 0.009)
MVP		0.26
MPC		1.4
ClinPred		0.59	D
GERP RS		2.3
Varity_R		0.082
gMVP		0.26
Mutation Taster		=95/5	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

hg19: chr8-126443154;