5-181195590-T-A

Variant names:

• chr5-181195590-T-A
• rs746514946
• NM_203293.3:c.1112A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203293.3(TRIM7):​c.1112A>T​(p.Gln371Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. Q371R) 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: 1.34
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26541167).

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.1112A>T	p.Gln371Leu	missense	Exon 7 of 7	NP_976038.1	Q9C029-2
	TRIM7	NM_203297.2		c.566A>T	p.Gln189Leu	missense	Exon 5 of 5	NP_976042.1	Q9C029-4
	TRIM7	NM_203294.2		c.488A>T	p.Gln163Leu	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.1112A>T	p.Gln371Leu	missense	Exon 7 of 7	ENSP00000274773.7	Q9C029-2
	TRIM7	ENST00000393319.7	TSL:1	c.566A>T	p.Gln189Leu	missense	Exon 5 of 5	ENSP00000376994.3	Q9C029-4
	TRIM7	ENST00000393315.5	TSL:1	c.488A>T	p.Gln163Leu	missense	Exon 7 of 7	ENSP00000376991.1	Q9C029-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444726 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 716154

African (AFR) AF: 0.00 AC: 0 AN: 32926

American (AMR) AF: 0.00 AC: 0 AN: 43154

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25516

East Asian (EAS) AF: 0.00 AC: 0 AN: 39258

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101120

Other (OTH) AF: 0.00 AC: 0 AN: 59458

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.081	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.10
Sift	Benign	0.042	D
Sift4G	Uncertain	0.039	D
Polyphen		0.025	B
Vest4		0.25
MutPred		0.48		Loss of disorder (P = 0.0575)
MVP		0.49
MPC		0.69
ClinPred		0.34	T
GERP RS		4.7
Varity_R		0.48
gMVP		0.71
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs746514946; hg19: chr5-180622590;