7-75399180-G-T

Position:

• chr7-75399180-G-T

Variant summary

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

The ENST00000323819.8(TRIM73):​c.247G>T​(p.Asp83Tyr) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D83A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 14)
• Consequence: TRIM73 ENST00000323819.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87

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 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=0.20089722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM73	NM_198924.4	c.247G>T	p.Asp83Tyr	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.247G>T	p.Asp83Tyr	missense_variant	2/5	1	NM_198924.4	ENSP00000318615.3
TRIM73	ENST00000447409.6	c.247G>T	p.Asp83Tyr	missense_variant	2/5	1		ENSP00000407135.2
TRIM73	ENST00000450434.5	c.-147G>T		5_prime_UTR_variant	2/5	1		ENSP00000394718.1
TRIM73	ENST00000430211.5	c.247G>T	p.Asp83Tyr	missense_variant	2/7	2		ENSP00000410121.1

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 14

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.247G>T (p.D83Y) alteration is located in exon 2 (coding exon 1) of the TRIM73 gene. This alteration results from a G to T substitution at nucleotide position 247, causing the aspartic acid (D) at amino acid position 83 to be replaced by a tyrosine (Y). 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	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.84	T;T;T;.
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M;.;.;M
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.3	N;N;D;N
REVEL	Benign	0.097
Sift	Uncertain	0.017	D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D
Polyphen		0.94	P;.;.;P
Vest4		0.26
MutPred		0.39		Loss of disorder (P = 0.0347);Loss of disorder (P = 0.0347);Loss of disorder (P = 0.0347);Loss of disorder (P = 0.0347);
MVP		0.34
ClinPred		0.76	D
GERP RS		2.3
Varity_R		0.13
gMVP		0.083

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1584621742; hg19: chr7-75028464;