chr5-181195515-C-G

Variant names:

• chr5-181195515-C-G
• rs762319634
• NM_203293.3:c.1187G>C

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.1187G>C​(p.Arg396Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98
• 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, 0.96

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.1187G>C	p.Arg396Pro	missense	Exon 7 of 7	NP_976038.1	Q9C029-2
	TRIM7	NM_203297.2		c.641G>C	p.Arg214Pro	missense	Exon 5 of 5	NP_976042.1	Q9C029-4
	TRIM7	NM_203294.2		c.563G>C	p.Arg188Pro	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.1187G>C	p.Arg396Pro	missense	Exon 7 of 7	ENSP00000274773.7	Q9C029-2
	TRIM7	ENST00000393319.7	TSL:1	c.641G>C	p.Arg214Pro	missense	Exon 5 of 5	ENSP00000376994.3	Q9C029-4
	TRIM7	ENST00000393315.5	TSL:1	c.563G>C	p.Arg188Pro	missense	Exon 7 of 7	ENSP00000376991.1	Q9C029-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000163 AC: 4 AN: 245108 AF XY: 0.0000224

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000221

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460278 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726492

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: 26104

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52428

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111560

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000249 AC: 3

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	0.82
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	0.31	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		5.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.83		Loss of catalytic residue at R396 (P = 0.0059)
MVP		0.86
MPC		2.0
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.94
gMVP		0.97
Mutation Taster		=63/37	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: rs762319634; hg19: chr5-180622515;