chr2-27305636-G-T

Variant names:

• chr2-27305636-G-T
• NM_187841.3:c.662G>T

Variant summary

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

The NM_187841.3(TRIM54):​c.662G>T​(p.Cys221Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,438 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM54 NM_187841.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602

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 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=0.09780747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM54	NM_187841.3	c.662G>T	p.Cys221Phe	missense_variant	Exon 5 of 9	ENST00000380075.7	NP_912730.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM54	ENST00000380075.7	c.662G>T	p.Cys221Phe	missense_variant	Exon 5 of 9	1	NM_187841.3	ENSP00000369415.3
TRIM54	ENST00000296098.4	c.788G>T	p.Cys263Phe	missense_variant	Exon 6 of 10	1		ENSP00000296098.4
TRIM54	ENST00000485306.1	n.452G>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
TRIM54	ENST00000488321.1	n.417G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461438 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.29	N;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	2.2	N;N
REVEL	Benign	0.075
Sift	Benign	0.34	T;T
Sift4G	Benign	0.51	T;T
Polyphen		0.0	B;B
Vest4		0.38
MutPred		0.46		Loss of catalytic residue at V223 (P = 0.0792);.;
MVP		0.43
MPC		0.23
ClinPred		0.31	T
GERP RS		4.9
Varity_R		0.13
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-27528504;