7-101088082-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030961.3(TRIM56):c.770A>G(p.Glu257Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000022 in 1,364,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: TRIM56 NM_030961.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.226

Genes affected

TRIM56 (HGNC:19028): (tripartite motif containing 56) Enables RNA binding activity. Predicted to be involved in several processes, including defense response to other organism; positive regulation of macromolecule metabolic process; and protein K63-linked ubiquitination. Predicted to be located in cytoplasm. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10731986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM56	NM_030961.3	c.770A>G	p.Glu257Gly	missense_variant	3/3	ENST00000306085.11
TRIM56	XM_011516589.4	c.770A>G	p.Glu257Gly	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM56	ENST00000306085.11	c.770A>G	p.Glu257Gly	missense_variant	3/3	1	NM_030961.3	P1
TRIM56	ENST00000412507.1	c.770A>G	p.Glu257Gly	missense_variant	3/4	1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000786 AC: 1 AN: 127278 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 68384

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: 0.00

Gnomad OTH exome AF: 0.000263

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1364026 Hom.: 0 Cov.: 29 AF XY: 0.00000299 AC XY: 2 AN XY: 669498

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: 0.0000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000353

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.770A>G (p.E257G) alteration is located in exon 3 (coding exon 1) of the TRIM56 gene. This alteration results from a A to G substitution at nucleotide position 770, causing the glutamic acid (E) at amino acid position 257 to be replaced by a glycine (G). 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	Benign	0.12
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
Cadd	Benign	21
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.
MutationTaster	Benign	0.93	D
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.0050	B;B
Vest4		0.12
MutPred		0.35		Gain of MoRF binding (P = 0.0396);Gain of MoRF binding (P = 0.0396);
MVP		0.63
MPC		1.5
ClinPred		0.28	T
GERP RS		2.7
Varity_R		0.12
gMVP		0.39

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: rs1193925069; hg19: chr7-100731363;