chr7-101087796-C-G

Variant names:

• chr7-101087796-C-G
• rs374323876
• NM_030961.3:c.484C>G

Variant summary

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

The NM_030961.3(TRIM56):​c.484C>G​(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R162W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRIM56 NM_030961.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• 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=0.30447203).

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.484C>G	p.Arg162Gly	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.484C>G	p.Arg162Gly	missense	Exon 3 of 3	ENSP00000305161.6	Q9BRZ2-1
	TRIM56	ENST00000412507.1	TSL:1	c.484C>G	p.Arg162Gly	missense	Exon 3 of 4	ENSP00000404186.1	C9JI91
	TRIM56	ENST00000877458.1		c.484C>G	p.Arg162Gly	missense	Exon 4 of 4	ENSP00000547517.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454040 Hom.: 0 Cov.: 29 AF XY: 0.00000277 AC XY: 2 AN XY: 723186

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25904

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 85788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110130

Other (OTH) AF: 0.00 AC: 0 AN: 60130

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.080
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.16
Sift	Benign	0.40	T
Sift4G	Uncertain	0.016	D
Polyphen		0.99	D
Vest4		0.30
MutPred		0.45		Loss of helix (P = 0.0558)
MVP		0.69
MPC		1.4
ClinPred		0.92	D
GERP RS		4.0
Varity_R		0.33
gMVP		0.69
Mutation Taster		=60/40	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: rs374323876; hg19: chr7-100731077;