11-89710670-C-A

Position:

• chr11-89710670-C-A

Variant summary

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

The NM_001146162.1(TRIM77):​c.372C>A​(p.His124Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: TRIM77 NM_001146162.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.102

Genes affected

TRIM77 (HGNC:34228): (tripartite motif containing 77) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [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=0.21904007).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM77	NM_001146162.1	c.372C>A	p.His124Gln	missense_variant	1/6	ENST00000398290.7	NP_001139634.1
TRIM77	NM_001271942.1	c.372C>A	p.His124Gln	missense_variant	1/5		NP_001258871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM77	ENST00000398290.7	c.372C>A	p.His124Gln	missense_variant	1/6	5	NM_001146162.1	ENSP00000474003	P1
TRIM77	ENST00000534392.4	c.21C>A	p.His7Gln	missense_variant	1/5	1		ENSP00000474353

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397870 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 689412

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jul 19, 2022

The c.372C>A (p.H124Q) alteration is located in exon 1 (coding exon 1) of the TRIM77 gene. This alteration results from a C to A substitution at nucleotide position 372, causing the histidine (H) at amino acid position 124 to be replaced by a glutamine (Q). 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	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	14
DANN	Benign	0.71
DEOGEN2	Benign	0.22	T;.
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.22	T;T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Benign	0.45	T
Sift4G	Uncertain	0.0040	D;D
Vest4		0.35
MVP		0.47
GERP RS		-0.017
Varity_R		0.082
gMVP		0.20

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: rs1387739490; hg19: chr11-89443838;