rs968020124

Variant names:

• chr8-125431155-G-A
• rs968020124
• NM_025195.4:c.253G>A

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.253G>A​(p.Ala85Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,155,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: TRIB1 NM_025195.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• 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=0.08606729).

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.253G>A	p.Ala85Thr	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.253G>A	p.Ala85Thr	missense	Exon 1 of 3	ENSP00000312150.3	Q96RU8-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000173 AC: 20 AN: 1155850 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 15 AN XY: 557512

African (AFR) AF: 0.00 AC: 0 AN: 23364

American (AMR) AF: 0.00 AC: 0 AN: 8732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15518

East Asian (EAS) AF: 0.00 AC: 0 AN: 27190

South Asian (SAS) AF: 0.00 AC: 0 AN: 37066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3180

European-Non Finnish (NFE) AF: 0.0000207 AC: 20 AN: 967730

Other (OTH) AF: 0.00 AC: 0 AN: 47058

GnomAD4 genome Cov.: 33

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	0.074
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.085	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.40	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.023
Sift	Benign	0.43	T
Sift4G	Benign	0.58	T
Polyphen		0.063	B
Vest4		0.098
MutPred		0.23		Gain of glycosylation at A85 (P = 0.0012)
MVP		0.34
MPC		0.44
ClinPred		0.11	T
GERP RS		1.2
Varity_R		0.036
gMVP		0.41
Mutation Taster		=89/11	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: rs968020124; hg19: chr8-126443397;