7-73312962-C-G

Position:

• chr7-73312962-C-G

Variant summary

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

The NM_178125.3(TRIM50):​c.1423G>C​(p.Gly475Arg) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM50 NM_178125.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.259

Genes affected

TRIM50 (HGNC:19017): (tripartite motif containing 50) Enables identical protein binding activity. Predicted to be involved in protein ubiquitination. Predicted to act upstream of or within regulation of establishment of protein localization. Located in cytosol. [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=0.10746923).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM50	NM_178125.3	c.1423G>C	p.Gly475Arg	missense_variant	7/7	ENST00000333149.7	NP_835226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM50	ENST00000333149.7	c.1423G>C	p.Gly475Arg	missense_variant	7/7	1	NM_178125.3	ENSP00000327994	P1
TRIM50	ENST00000453152.1	c.1423G>C	p.Gly475Arg	missense_variant	7/7	2		ENSP00000413875	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

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

Aug 26, 2022

The c.1423G>C (p.G475R) alteration is located in exon 7 (coding exon 6) of the TRIM50 gene. This alteration results from a G to C substitution at nucleotide position 1423, causing the glycine (G) at amino acid position 475 to be replaced by an arginine (R). 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	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	0.80	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.086
Sift	Uncertain	0.0060	D;D
Sift4G	Benign	0.32	T;T
Vest4		0.095
MutPred		0.18		Loss of glycosylation at S480 (P = 0.1092);Loss of glycosylation at S480 (P = 0.1092);
MVP		0.68
MPC		0.30
ClinPred		0.38	T
GERP RS		4.0
gMVP		0.47

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: rs1184355389; hg19: chr7-72726958;