chr8-66150406-C-A

Position:

• chr8-66150406-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_184085.2(TRIM55):​c.925C>A​(p.His309Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TRIM55 NM_184085.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.93

Genes affected

TRIM55 (HGNC:14215): (tripartite motif containing 55) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This protein associates transiently with microtubules, myosin, and titin during muscle sarcomere assembly. It may act as a transient adaptor and plays a regulatory role in the assembly of sarcomeres. Four alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2809097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM55	NM_184085.2	c.925C>A	p.His309Asn	missense_variant	7/10	ENST00000315962.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM55	ENST00000315962.9	c.925C>A	p.His309Asn	missense_variant	7/10	1	NM_184085.2	A1
TRIM55	ENST00000276573.11	c.925C>A	p.His309Asn	missense_variant	7/11	1		A1
TRIM55	ENST00000353317.9	c.925C>A	p.His309Asn	missense_variant	7/9	1		P4
TRIM55	ENST00000350034.4	c.603+13216C>A		intron_variant		1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Jun 07, 2024

The c.925C>A (p.H309N) alteration is located in exon 7 (coding exon 7) of the TRIM55 gene. This alteration results from a C to A substitution at nucleotide position 925, causing the histidine (H) at amino acid position 309 to be replaced by an asparagine (N). 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	0.094
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Uncertain	0.61	.;D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.25	T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L;L
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.077
Sift	Benign	0.037	D;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.0030	B;B;B
Vest4		0.49
MutPred		0.38		Gain of disorder (P = 0.0808);Gain of disorder (P = 0.0808);Gain of disorder (P = 0.0808);
MVP		0.40
MPC		0.041
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.19

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: chr8-67062641;