NM_001012414.3:c.526-2087T>G

Variant names:

• chr4-164957183-A-C
• rs3733418
• ENST00000329314.6:c.526-2087T>G

Variant summary

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

The NM_001012414.3(TRIM61):​c.526-2087T>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM61 NM_001012414.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 0 publications found

Genes affected

TRIM61 (HGNC:24339): (tripartite motif containing 61) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM218A (HGNC:26466): (family with sequence similarity 218 member A)

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=0.04165563).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012414.3. 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
	TRIM61	NM_001012414.3		c.526-2087T>G		intron	N/A	NP_001012414.1	Q5EBN2
	FAM218A	NR_160935.1		n.236A>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM61	ENST00000329314.6	TSL:1	c.526-2087T>G		intron	N/A	ENSP00000332288.5	Q5EBN2
	FAM218A	ENST00000648094.2		n.238A>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.0
DANN	Benign	0.26
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.7
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.063
Polyphen		0.0	B
Vest4		0.093
MutPred		0.20		Loss of sheet (P = 0.0228)
MVP		0.014
MPC		1.1
ClinPred		0.056	T
GERP RS		-1.1
Varity_R		0.34
gMVP		0.024

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3733418; hg19: chr4-165878335;