chr7-99903255-C-G

Position:

• chr7-99903255-C-G

Variant summary

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

The NM_033091.3(TRIM4):​c.804G>C​(p.Gln268His) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRIM4 NM_033091.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.374

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=0.05891359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM4	NM_033091.3	c.804G>C	p.Gln268His	missense_variant	5/6	ENST00000349062.7	NP_149082.1
TRIM4	NM_033017.4	c.882G>C	p.Gln294His	missense_variant	6/7		NP_148977.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM4	ENST00000349062.7	c.804G>C	p.Gln268His	missense_variant	5/6	1	NM_033091.3	ENSP00000275736	P2
TRIM4	ENST00000355947.6	c.882G>C	p.Gln294His	missense_variant	6/7	1		ENSP00000348216	A2
TRIM4	ENST00000354241.5	c.804G>C	p.Gln268His	missense_variant	5/6	1		ENSP00000346186
TRIM4	ENST00000447480.5	c.510G>C	p.Gln170His	missense_variant	5/6	3		ENSP00000396229

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Oct 26, 2021

The c.882G>C (p.Q294H) alteration is located in exon 6 (coding exon 6) of the TRIM4 gene. This alteration results from a G to C substitution at nucleotide position 882, causing the glutamine (Q) at amino acid position 294 to be replaced by a histidine (H). 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	0.27
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.0063	T;.;.
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.60	N;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.020
Sift	Benign	0.058	T;T;D
Sift4G	Benign	0.090	T;T;T
Polyphen		0.053	B;B;B
Vest4		0.073
MutPred		0.50		Loss of helix (P = 0.0558);.;.;
MVP		0.099
MPC		0.20
ClinPred		0.068	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.072
gMVP		0.16

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: chr7-99500878;