2-27282741-A-T

Variant names:

• chr2-27282741-A-T
• rs754426349
• NM_187841.3:c.10A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_187841.3(TRIM54):​c.10A>T​(p.Thr4Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T4I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM54 NM_187841.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 0 publications found

Genes affected

TRIM54 (HGNC:16008): (tripartite motif containing 54) The protein encoded by this gene contains a RING finger motif and is highly similar to the ring finger proteins RNF28/MURF1 and RNF29/MURF2. In vitro studies demonstrated that this protein, RNF28, and RNF29 form heterodimers, which may be important for the regulation of titin kinase and microtubule-dependent signal pathways in striated muscles. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038831085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_187841.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM54	NM_187841.3	MANE Select	c.10A>T	p.Thr4Ser	missense	Exon 1 of 9	NP_912730.2	Q9BYV2-1
	TRIM54	NM_032546.4		c.10A>T	p.Thr4Ser	missense	Exon 1 of 10	NP_115935.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM54	ENST00000380075.7	TSL:1 MANE Select	c.10A>T	p.Thr4Ser	missense	Exon 1 of 9	ENSP00000369415.3	Q9BYV2-1
	TRIM54	ENST00000296098.4	TSL:1	c.10A>T	p.Thr4Ser	missense	Exon 1 of 10	ENSP00000296098.4	Q9BYV2-2
	TRIM54	ENST00000884197.1		c.10A>T	p.Thr4Ser	missense	Exon 1 of 10	ENSP00000554256.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.8
DANN	Benign	0.81
DEOGEN2	Benign	0.065	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.063
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.042
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.18		Gain of disorder (P = 0.0452)
MVP		0.34
MPC		0.18
ClinPred		0.070	T
GERP RS		-1.0
PromoterAI		-0.013	Neutral
Varity_R		0.045
gMVP		0.26
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs754426349; hg19: chr2-27505609;