chr7-99892411-T-C

Position:

• chr7-99892411-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033091.3(TRIM4):​c.1177A>G​(p.Ile393Val) 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. 16/21 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: -2.36

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05302167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM4	NM_033091.3	c.1177A>G	p.Ile393Val	missense_variant	6/6	ENST00000349062.7	NP_149082.1
TRIM4	NM_033017.4	c.1255A>G	p.Ile419Val	missense_variant	7/7		NP_148977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM4	ENST00000349062.7	c.1177A>G	p.Ile393Val	missense_variant	6/6	1	NM_033091.3	ENSP00000275736.4
TRIM4	ENST00000355947.6	c.1255A>G	p.Ile419Val	missense_variant	7/7	1		ENSP00000348216.2
TRIM4	ENST00000447480.5	c.544+10807A>G		intron_variant		3		ENSP00000396229.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 11, 2024

The c.1255A>G (p.I419V) alteration is located in exon 7 (coding exon 7) of the TRIM4 gene. This alteration results from a A to G substitution at nucleotide position 1255, causing the isoleucine (I) at amino acid position 419 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.10
DANN	Benign	0.12
DEOGEN2	Benign	0.0035	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0049	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.59	N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.25	N;N
REVEL	Benign	0.033
Sift	Benign	0.62	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.025	B;B
Vest4		0.031
MutPred		0.50		Gain of sheet (P = 0.0827);.;
MVP		0.26
MPC		0.18
ClinPred		0.043	T
GERP RS		-1.4
Varity_R		0.036
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-99490034;