chr1-231163345-C-G

Variant names:

• chr1-231163345-C-G
• rs1682348222
• NM_001004342.5:c.376C>G

Variant summary

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

The NM_001004342.5(TRIM67):​c.376C>G​(p.Arg126Gly) 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: 33)
• Consequence: TRIM67 NM_001004342.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54
• Publications: 0 publications found

Genes affected

TRIM67 (HGNC:31859): (tripartite motif containing 67) Predicted to enable zinc ion binding activity. Predicted to be involved in regulation of protein localization. Predicted to act upstream of or within negative regulation of Ras protein signal transduction; positive regulation of neuron projection development; and positive regulation of ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000295849 (HGNC:):

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=0.19076997).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004342.5. 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
	TRIM67	NM_001004342.5	MANE Select	c.376C>G	p.Arg126Gly	missense	Exon 1 of 10	NP_001004342.3
	TRIM67	NM_001410937.1		c.376C>G	p.Arg126Gly	missense	Exon 1 of 10	NP_001397866.1	F8W8C1
	TRIM67	NM_001300889.3		c.256C>G	p.Arg86Gly	missense	Exon 2 of 12	NP_001287818.1	Q6ZTA4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM67	ENST00000366653.6	TSL:1 MANE Select	c.376C>G	p.Arg126Gly	missense	Exon 1 of 10	ENSP00000355613.5	Q6ZTA4-3
	TRIM67	ENST00000449018.7	TSL:1	c.256C>G	p.Arg86Gly	missense	Exon 2 of 12	ENSP00000400163.3	Q6ZTA4-2
	TRIM67	ENST00000444294.7	TSL:5	c.376C>G	p.Arg126Gly	missense	Exon 1 of 10	ENSP00000412124.3	F8W8C1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.075
FATHMM_MKL	Benign	0.51	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.5
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.18
Sift	Benign	0.12	T
Sift4G	Benign	0.42	T
Polyphen		0.12	B
Vest4		0.37
MutPred		0.36		Gain of catalytic residue at V127 (P = 0.0229)
MVP		0.10
MPC		1.7
ClinPred		0.82	D
GERP RS		4.0
PromoterAI		0.046	Neutral
Varity_R		0.23
gMVP		0.56
Mutation Taster		=40/60	disease causing

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: rs1682348222; hg19: chr1-231299091;