NM_030961.3:c.601C>T

Variant names:

• chr7-101087913-C-T
• rs756994253
• NM_030961.3:c.601C>T

Variant summary

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

The NM_030961.3(TRIM56):​c.601C>T​(p.Pro201Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM56 NM_030961.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.42
• Publications: 0 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: 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=0.3107587).

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.601C>T	p.Pro201Ser	missense	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.601C>T	p.Pro201Ser	missense	Exon 3 of 3	ENSP00000305161.6	Q9BRZ2-1
	TRIM56	ENST00000412507.1	TSL:1	c.601C>T	p.Pro201Ser	missense	Exon 3 of 4	ENSP00000404186.1	C9JI91
	TRIM56	ENST00000877458.1		c.601C>T	p.Pro201Ser	missense	Exon 4 of 4	ENSP00000547517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000438 AC: 1 AN: 228564 AF XY: 0.00

Gnomad AFR exome AF: 0.0000729

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000829 AC: 1

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	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.35	N
PhyloP100		1.4
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.20
Sift	Benign	0.063	T
Sift4G	Uncertain	0.023	D
Polyphen		0.99	D
Vest4		0.27
MutPred		0.41		Loss of catalytic residue at P201 (P = 2e-04)
MVP		0.61
MPC		1.4
ClinPred		0.32	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.066
gMVP		0.44
Mutation Taster		=91/9	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: rs756994253; hg19: chr7-100731194;