chr17-75875015-G-A

Position:

• chr17-75875015-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_033452.3(TRIM47):​c.1385C>T​(p.Pro462Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000014 (0 hom.)
• Consequence: TRIM47 NM_033452.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

Genes affected

TRIM47 (HGNC:19020): (tripartite motif containing 47) Enables ubiquitin-protein transferase activity. Involved in protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TRIM47 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.813

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM47	NM_033452.3	c.1385C>T	p.Pro462Leu	missense_variant	6/6	ENST00000254816.6	NP_258411.2
TRIM47	XM_005257787.5	c.671C>T	p.Pro224Leu	missense_variant	6/6		XP_005257844.1
TRIM47	XM_005257788.6	c.671C>T	p.Pro224Leu	missense_variant	6/6		XP_005257845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM47	ENST00000254816.6	c.1385C>T	p.Pro462Leu	missense_variant	6/6	1	NM_033452.3	ENSP00000254816.1
TRIM47	ENST00000587339.2	n.*688C>T		non_coding_transcript_exon_variant	6/6	1		ENSP00000465010.2
TRIM47	ENST00000587339.2	n.*688C>T		3_prime_UTR_variant	6/6	1		ENSP00000465010.2
TRIM47	ENST00000592942.1	n.301C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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: 0.00000180

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

Aug 14, 2024

The c.1385C>T (p.P462L) alteration is located in exon 6 (coding exon 6) of the TRIM47 gene. This alteration results from a C to T substitution at nucleotide position 1385, causing the proline (P) at amino acid position 462 to be replaced by a leucine (L). 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	0.14
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.60		Loss of catalytic residue at P462 (P = 0.0036);
MVP		0.81
MPC		0.41
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: chr17-73871096;