NM_030961.3:c.519C>T

Variant names:

• chr7-101087831-C-T
• rs145410552
• NM_030961.3:c.519C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_030961.3(TRIM56):​c.519C>T​(p.Pro173Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00145 in 1,603,680 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (2 hom.)
• Consequence: TRIM56 NM_030961.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -9.71
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-101087831-C-T is Benign according to our data. Variant chr7-101087831-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-9.71 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030961.3. 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
	TRIM56	NM_030961.3	MANE Select	c.519C>T	p.Pro173Pro	synonymous	Exon 3 of 3	NP_112223.1	Q9BRZ2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM56	ENST00000306085.11	TSL:1 MANE Select	c.519C>T	p.Pro173Pro	synonymous	Exon 3 of 3	ENSP00000305161.6	Q9BRZ2-1
	TRIM56	ENST00000412507.1	TSL:1	c.519C>T	p.Pro173Pro	synonymous	Exon 3 of 4	ENSP00000404186.1	C9JI91
	TRIM56	ENST00000877458.1		c.519C>T	p.Pro173Pro	synonymous	Exon 4 of 4	ENSP00000547517.1

Frequencies

GnomAD3 genomes AF: 0.00161 AC: 245 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00118 AC: 277 AN: 234890 AF XY: 0.00117

Gnomad AFR exome AF: 0.00273

Gnomad AMR exome AF: 0.000207

Gnomad ASJ exome AF: 0.000629

Gnomad EAS exome AF: 0.00119

Gnomad FIN exome AF: 0.00225

Gnomad NFE exome AF: 0.00146

Gnomad OTH exome AF: 0.00138

GnomAD4 exome AF: 0.00143 AC: 2079 AN: 1451398 Hom.: 2 Cov.: 29 AF XY: 0.00136 AC XY: 983 AN XY: 721498

African (AFR) AF: 0.00156 AC: 52 AN: 33364

American (AMR) AF: 0.000339 AC: 15 AN: 44296

Ashkenazi Jewish (ASJ) AF: 0.000465 AC: 12 AN: 25794

East Asian (EAS) AF: 0.00149 AC: 59 AN: 39526

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85612

European-Finnish (FIN) AF: 0.00197 AC: 96 AN: 48624

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5746

European-Non Finnish (NFE) AF: 0.00157 AC: 1744 AN: 1108374

Other (OTH) AF: 0.00152 AC: 91 AN: 60062

GnomAD4 genome AF: 0.00166 AC: 253 AN: 152282 Hom.: 1 Cov.: 33 AF XY: 0.00171 AC XY: 127 AN XY: 74466

African (AFR) AF: 0.00241 AC: 100 AN: 41568

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 67996

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.00139

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.056
DANN	Benign	0.70
PhyloP100		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	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: rs145410552; hg19: chr7-100731112; COSMIC: COSV60162143; COSMIC: COSV60162143;