5-181195516-G-C

Variant names:

• chr5-181195516-G-C
• rs991138763
• NM_203293.3:c.1186C>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_203293.3(TRIM7):​c.1186C>G​(p.Arg396Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R396W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIM7 NM_203293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.967

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.1186C>G	p.Arg396Gly	missense	Exon 7 of 7	NP_976038.1	Q9C029-2
	TRIM7	NM_203297.2		c.640C>G	p.Arg214Gly	missense	Exon 5 of 5	NP_976042.1	Q9C029-4
	TRIM7	NM_203294.2		c.562C>G	p.Arg188Gly	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.1186C>G	p.Arg396Gly	missense	Exon 7 of 7	ENSP00000274773.7	Q9C029-2
	TRIM7	ENST00000393319.7	TSL:1	c.640C>G	p.Arg214Gly	missense	Exon 5 of 5	ENSP00000376994.3	Q9C029-4
	TRIM7	ENST00000393315.5	TSL:1	c.562C>G	p.Arg188Gly	missense	Exon 7 of 7	ENSP00000376991.1	Q9C029-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460274 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726466

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111556

Other (OTH) AF: 0.0000166 AC: 1 AN: 60342

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Benign	0.087
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	4.0	H
PhyloP100		0.062
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.82
MutPred		0.86		Loss of stability (P = 0.038)
MVP		0.80
MPC		1.9
ClinPred		0.99	D
GERP RS		1.7
Varity_R		0.73
gMVP		0.93
Mutation Taster		=75/25	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

dbSNP: rs991138763; hg19: chr5-180622516;