2-27282741-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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

Verdict is Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM54	NM_187841.3	c.10A>T	p.Thr4Ser	missense_variant	Exon 1 of 9	ENST00000380075.7	NP_912730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM54	ENST00000380075.7	c.10A>T	p.Thr4Ser	missense_variant	Exon 1 of 9	1	NM_187841.3	ENSP00000369415.3
TRIM54	ENST00000296098.4	c.10A>T	p.Thr4Ser	missense_variant	Exon 1 of 10	1		ENSP00000296098.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.039	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.48	N;N
REVEL	Benign	0.042
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.10
MutPred		0.18		Gain of disorder (P = 0.0452);Gain of disorder (P = 0.0452);
MVP		0.34
MPC		0.18
ClinPred		0.070	T
GERP RS		-1.0
Varity_R		0.045
gMVP		0.26

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: rs754426349; hg19: chr2-27505609;