chr5-181195622-A-T

Variant names:

• chr5-181195622-A-T
• rs1271757829
• NM_203293.3:c.1080T>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203293.3(TRIM7):​c.1080T>A​(p.Asp360Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,984 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TRIM7 NM_203293.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.22

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM7	NM_203293.3	c.1080T>A	p.Asp360Glu	missense_variant	Exon 7 of 7	ENST00000274773.12	NP_976038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM7	ENST00000274773.12	c.1080T>A	p.Asp360Glu	missense_variant	Exon 7 of 7	1	NM_203293.3	ENSP00000274773.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000475 AC: 1 AN: 210568 Hom.: 0 AF XY: 0.00000880 AC XY: 1 AN XY: 113632

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406984 Hom.: 0 Cov.: 31 AF XY: 0.00000144 AC XY: 1 AN XY: 692856

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.25e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1080T>A (p.D360E) alteration is located in exon 7 (coding exon 7) of the TRIM7 gene. This alteration results from a T to A substitution at nucleotide position 1080, causing the aspartic acid (D) at amino acid position 360 to be replaced by a glutamic acid (E). 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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.79	T;T;T;.
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	2.0	M;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.4	D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		1.0	D;.;D;.
Vest4		0.42
MutPred		0.57		Gain of sheet (P = 0.1208);.;.;.;
MVP		0.62
MPC		1.6
ClinPred		0.93	D
GERP RS		4.6
Varity_R		0.81
gMVP		0.63

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

LitVar

Other links and lift over

dbSNP: rs1271757829; hg19: chr5-180622622;