chr7-99892208-A-C

Variant names:

• chr7-99892208-A-C
• NM_033091.3:c.1380T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033091.3(TRIM4):​c.1380T>G​(p.Ser460Arg) 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. 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: 32)
• Consequence: TRIM4 NM_033091.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0940
• Publications: 0 publications found

Genes affected

TRIM4 (HGNC:16275): (tripartite motif containing 4) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The protein localizes to cytoplasmic bodies. Its function has not been identified. Alternatively spliced transcript variants that encode different isoforms have been described.[provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33945942).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033091.3. 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
	TRIM4	NM_033091.3	MANE Select	c.1380T>G	p.Ser460Arg	missense	Exon 6 of 6	NP_149082.1	Q9C037-2
	TRIM4	NM_033017.4		c.1458T>G	p.Ser486Arg	missense	Exon 7 of 7	NP_148977.2	Q9C037-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM4	ENST00000349062.7	TSL:1 MANE Select	c.1380T>G	p.Ser460Arg	missense	Exon 6 of 6	ENSP00000275736.4	Q9C037-2
	TRIM4	ENST00000355947.6	TSL:1	c.1458T>G	p.Ser486Arg	missense	Exon 7 of 7	ENSP00000348216.2	Q9C037-1
	TRIM4	ENST00000953520.1		c.1398T>G	p.Ser466Arg	missense	Exon 6 of 6	ENSP00000623579.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.93
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.094
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.39
Sift	Benign	0.073	T
Sift4G	Benign	0.064	T
Polyphen		0.96	D
Vest4		0.41
MutPred		0.65		Gain of glycosylation at S490 (P = 0.1579)
MVP		0.45
MPC		0.84
ClinPred		0.75	D
GERP RS		1.4
Varity_R		0.11
gMVP		0.71
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

hg19: chr7-99489831;