rs3733418

chr4-164957183-A-Gchr4-164957183-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012414.3(TRIM61):c.526-2087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,612,466 control chromosomes in the GnomAD database, including 32,044 homozygotes. 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: 𝑓 0.16 (2804 hom., cov: 32)
  • Exomes 𝑓: 0.18 (29240 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.5631556E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM61	NM_001012414.3	c.526-2087T>C		intron_variant
FAM218A	NR_160935.1	n.236A>G		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>C		intron_variant		1
FAM218A	ENST00000648094.1	n.236A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24233 AN: 152016 Hom.: 2801 Cov.: 32

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.219 AC: 54324 AN: 247604 Hom.: 8047 AF XY: 0.223 AC XY: 29928 AN XY: 134072

Gnomad AFR exome AF: 0.0791

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.615

Gnomad SAS exome AF: 0.337

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.204

GnomAD4 exome AF: 0.179 AC: 261179 AN: 1460332 Hom.: 29240 Cov.: 32 AF XY: 0.184 AC XY: 133513 AN XY: 726338

Gnomad4 AFR exome AF: 0.0772

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.596

Gnomad4 SAS exome AF: 0.335

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.159 AC: 24245 AN: 152134 Hom.: 2804 Cov.: 32 AF XY: 0.164 AC XY: 12228 AN XY: 74374

Gnomad4 AFR AF: 0.0802

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.203

Alfa AF: 0.170 Hom.: 6968

Bravo AF: 0.160

TwinsUK AF: 0.148 AC: 547

ALSPAC AF: 0.142 AC: 549

ESP6500AA AF: 0.0790 AC: 348

ESP6500EA AF: 0.151 AC: 1298

ExAC AF: 0.212 AC: 25701

Asia WGS AF: 0.495 AC: 1720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.0
Dann	Benign	0.33
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0000076	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	P;P
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.074
Polyphen		0.048	B
Vest4		0.011
MPC		0.91
ClinPred		0.0024	T
GERP RS		-1.1
Varity_R		0.23
gMVP		0.010

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

LitVar

Other links and lift over

dbSNP: rs3733418; hg19: chr4-165878335;