1-33159854-C-T

Position:

• chr1-33159854-C-T

Variant summary

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

The NM_018207.3(TRIM62):​c.595G>A​(p.Glu199Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM62 NM_018207.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.95

Genes affected

TRIM62 (HGNC:25574): (tripartite motif containing 62) Enables identical protein binding activity; transcription coactivator activity; and ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of viral transcription; positive regulation of NF-kappaB transcription factor activity; and positive regulation of antifungal innate immune response. Is active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

AZIN2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM62	NM_018207.3	c.595G>A	p.Glu199Lys	missense_variant	3/5	ENST00000291416.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM62	ENST00000291416.10	c.595G>A	p.Glu199Lys	missense_variant	3/5	1	NM_018207.3	P1
TRIM62	ENST00000543586.1	c.232G>A	p.Glu78Lys	missense_variant	3/5	2
TRIM62	ENST00000485148.1	n.644G>A		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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

Oct 05, 2023

The c.595G>A (p.E199K) alteration is located in exon 3 (coding exon 3) of the TRIM62 gene. This alteration results from a G to A substitution at nucleotide position 595, causing the glutamic acid (E) at amino acid position 199 to be replaced by a lysine (K). 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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.026	T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.016	T
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.98	N;N
REVEL	Benign	0.20
Sift	Benign	0.40	T;D
Sift4G	Benign	0.095	T;T
Polyphen		0.89	P;.
Vest4		0.85
MutPred		0.49		Gain of MoRF binding (P = 0.0038);.;
MVP		0.66
MPC		1.0
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.26
gMVP		0.40

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-33625455;