rs767050256

Variant names:

• chr8-125431086-C-A
• rs767050256
• NM_025195.4:c.184C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-125431086-C-A
• chr8-125431086-C-T
• chr8-125431086-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025195.4(TRIB1):​c.184C>A​(p.Pro62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000785 in 1,389,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P62S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: TRIB1 NM_025195.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.525
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04779601).

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.184C>A	p.Pro62Thr	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.184C>A	p.Pro62Thr	missense	Exon 1 of 3	ENSP00000312150.3	Q96RU8-1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152016 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000989 AC: 2 AN: 20220 AF XY: 0.000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000768 AC: 95 AN: 1237266 Hom.: 0 Cov.: 29 AF XY: 0.0000743 AC XY: 45 AN XY: 605444

African (AFR) AF: 0.0000820 AC: 2 AN: 24376

American (AMR) AF: 0.000142 AC: 2 AN: 14068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18600

East Asian (EAS) AF: 0.000109 AC: 3 AN: 27404

South Asian (SAS) AF: 0.0000691 AC: 4 AN: 57852

European-Finnish (FIN) AF: 0.0000325 AC: 1 AN: 30738

Middle Eastern (MID) AF: 0.000281 AC: 1 AN: 3562

European-Non Finnish (NFE) AF: 0.0000753 AC: 76 AN: 1009838

Other (OTH) AF: 0.000118 AC: 6 AN: 50828

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152016 Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9 AN XY: 74268

African (AFR) AF: 0.0000725 AC: 3 AN: 41400

American (AMR) AF: 0.000524 AC: 8 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000831

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	0.079
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N
PhyloP100		0.53
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.024
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.18	T
Polyphen		0.041	B
Vest4		0.17
MutPred		0.21		Gain of phosphorylation at P62 (P = 0.0103)
MVP		0.23
MPC		0.52
ClinPred		0.047	T
GERP RS		1.6
Varity_R		0.13
gMVP		0.35
Mutation Taster		=93/7	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: rs767050256; hg19: chr8-126443328;