4-164957183-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001012414.3(TRIM61):c.526-2087T>A 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

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

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=0.040701956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM61	NM_001012414.3	c.526-2087T>A		intron_variant
FAM218A	NR_160935.1	n.236A>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM61	ENST00000329314.6	c.526-2087T>A		intron_variant		1
FAM218A	ENST00000648094.1	n.236A>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000258 Hom.: 6968

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	6.4
Dann	Benign	0.48
DEOGEN2	Benign	0.054	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.060
Polyphen		0.0	B
Vest4		0.044
MutPred		0.25		Gain of glycosylation at S56 (P = 0.0372);
MVP		0.030
MPC		0.92
ClinPred		0.058	T
GERP RS		-1.1
Varity_R		0.29
gMVP		0.0093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3733418; hg19: chr4-165878335;