5-181195596-C-T

Variant names:

• chr5-181195596-C-T
• rs768191915
• NM_203293.3:c.1106G>A

Variant summary

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

The NM_203293.3(TRIM7):​c.1106G>A​(p.Arg369Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,440,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R369L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIM7 NM_203293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 0 publications found

Genes affected

TRIM7 (HGNC:16278): (tripartite motif containing 7) 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, a B-box type 2, and a coiled-coil region. The protein localizes to both the nucleus and the cytoplasm, and may represent a participant in the initiation of glycogen synthesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

TRIM7-AS1 (HGNC:40764): (TRIM7 antisense RNA 1)

TRIM7-AS2 (HGNC:56031): (TRIM7 antisense RNA 2)

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=0.069143176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203293.3. 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
	TRIM7	NM_203293.3	MANE Select	c.1106G>A	p.Arg369Gln	missense	Exon 7 of 7	NP_976038.1	Q9C029-2
	TRIM7	NM_203297.2		c.560G>A	p.Arg187Gln	missense	Exon 5 of 5	NP_976042.1	Q9C029-4
	TRIM7	NM_203294.2		c.482G>A	p.Arg161Gln	missense	Exon 7 of 7	NP_976039.1	Q9C029-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM7	ENST00000274773.12	TSL:1 MANE Select	c.1106G>A	p.Arg369Gln	missense	Exon 7 of 7	ENSP00000274773.7	Q9C029-2
	TRIM7	ENST00000393319.7	TSL:1	c.560G>A	p.Arg187Gln	missense	Exon 5 of 5	ENSP00000376994.3	Q9C029-4
	TRIM7	ENST00000393315.5	TSL:1	c.482G>A	p.Arg161Gln	missense	Exon 7 of 7	ENSP00000376991.1	Q9C029-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 235538 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1440170 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 713404

African (AFR) AF: 0.0000305 AC: 1 AN: 32768

American (AMR) AF: 0.00 AC: 0 AN: 42616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25238

East Asian (EAS) AF: 0.00 AC: 0 AN: 39188

South Asian (SAS) AF: 0.00 AC: 0 AN: 84578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098590

Other (OTH) AF: 0.00 AC: 0 AN: 59218

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0069	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.056
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.014
Sift	Benign	0.066	T
Sift4G	Benign	0.53	T
Polyphen		0.069	B
Vest4		0.086
MutPred		0.33		Loss of MoRF binding (P = 0.1756)
MVP		0.15
MPC		0.89
ClinPred		0.21	T
GERP RS		2.0
Varity_R		0.064
gMVP		0.36
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs768191915; hg19: chr5-180622596;