7-75399181-A-C

Position:

• chr7-75399181-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198924.4(TRIM73):​c.248A>C​(p.Asp83Ala) 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: 13)
• Consequence: TRIM73 NM_198924.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.436

Genes affected

TRIM73 (HGNC:18162): (tripartite motif containing 73) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062218785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM73	NM_198924.4	c.248A>C	p.Asp83Ala	missense_variant	2/5	ENST00000323819.8	NP_944606.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM73	ENST00000323819.8	c.248A>C	p.Asp83Ala	missense_variant	2/5	1	NM_198924.4	ENSP00000318615	P2
TRIM73	ENST00000447409.6	c.248A>C	p.Asp83Ala	missense_variant	2/5	1		ENSP00000407135
TRIM73	ENST00000450434.5	c.-146A>C		5_prime_UTR_variant	2/5	1		ENSP00000394718
TRIM73	ENST00000430211.5	c.248A>C	p.Asp83Ala	missense_variant	2/7	2		ENSP00000410121	A2

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 13

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 12, 2021

The c.248A>C (p.D83A) alteration is located in exon 2 (coding exon 1) of the TRIM73 gene. This alteration results from a A to C substitution at nucleotide position 248, causing the aspartic acid (D) at amino acid position 83 to be replaced by an alanine (A). 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	0.10
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.011	T;.;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.58	T;T;T;.
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.062	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.99	L;.;.;L
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.13	T;T;T;T
Sift4G	Uncertain	0.048	D;D;D;D
Polyphen		0.0020	B;.;.;B
Vest4		0.075
MutPred		0.30		Loss of ubiquitination at K87 (P = 0.0534);Loss of ubiquitination at K87 (P = 0.0534);Loss of ubiquitination at K87 (P = 0.0534);Loss of ubiquitination at K87 (P = 0.0534);
MVP		0.18
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.098
gMVP		0.038

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1584621745; hg19: chr7-75028465;