dbSNP rs1442901519: TRIM56:p.Arg310Ser (chr7-101088240-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_030961.3(TRIM56):c.928C>A(p.Arg310Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000076 in 1,316,256 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. R310H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

TRIM56
NM_030961.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.82

Publications

0 publications found

Variant links:

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]

TRIM56 links:

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ACMG classification

Classification was made for transcript

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=0.34110337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM56	NM_030961.3 link	c.928C>A	p.Arg310Ser	missense_variant	Exon 3 of 3	ENST00000306085.11	NP_112223.1	Q9BRZ2-1
TRIM56	XM_011516589.4 link	c.928C>A	p.Arg310Ser	missense_variant	Exon 2 of 2		XP_011514891.1	Q9BRZ2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM56	ENST00000306085.11 link	c.928C>A	p.Arg310Ser	missense_variant	Exon 3 of 3	1	NM_030961.3	ENSP00000305161.6		Q9BRZ2-1
TRIM56	ENST00000412507.1 link	c.816+112C>A		intron_variant	Intron 3 of 3	1		ENSP00000404186.1		C9JI91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.60e-7

AC:

AN:

1316256

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

642702

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29472

American (AMR)

AF:

0.00

AC:

AN:

23470

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19984

East Asian (EAS)

AF:

0.00

AC:

AN:

35774

South Asian (SAS)

AF:

0.0000148

AC:

AN:

67352

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4576

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1047984

Other (OTH)

AF:

0.00

AC:

AN:

54642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.71

M_CAP

Benign

0.017

MetaRNN

Benign

0.34

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.8

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.7

REVEL

Benign

0.12

Sift

Uncertain

0.022

Sift4G

Uncertain

0.0070

Polyphen

0.65

Vest4

0.37

MutPred

0.48

Gain of glycosylation at R310 (P = 0.0292);

MVP

0.57

MPC

0.95

ClinPred

0.28

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.23

gMVP

0.35

Mutation Taster

=79/21

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over