chr2-95481618-T-C

Position:

• chr2-95481618-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001164464.2(TRIM43B):​c.484A>G​(p.Arg162Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000993 in 1,460,204 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000099 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM43B NM_001164464.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.357

Genes affected

TRIM43B (HGNC:37146): (tripartite motif containing 43B) 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026144654).
• BS2: High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM43B	NM_001164464.2	c.484A>G	p.Arg162Gly	missense_variant	3/7	ENST00000639673.3	NP_001157936.1
TRIM43B	XM_011511669.2	c.514A>G	p.Arg172Gly	missense_variant	3/7		XP_011509971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM43B	ENST00000639673.3	c.484A>G	p.Arg162Gly	missense_variant	3/7	1	NM_001164464.2	ENSP00000492719.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 28 AN: 151962 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.000411

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000129 AC: 32 AN: 248542 Hom.: 1 AF XY: 0.000134 AC XY: 18 AN XY: 134606

Gnomad AFR exome AF: 0.000445

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000132

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000534

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.0000993 AC: 145 AN: 1460204 Hom.: 2 Cov.: 30 AF XY: 0.000105 AC XY: 76 AN XY: 726286

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000494

Gnomad4 ASJ exome AF: 0.0000767

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000105

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000801

Gnomad4 OTH exome AF: 0.000133

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000191 AC: 29 AN: 152078 Hom.: 0 Cov.: 30 AF XY: 0.000229 AC XY: 17 AN XY: 74374

Gnomad4 AFR AF: 0.000410

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000432 Hom.: 0

ExAC AF: 0.000115 AC: 14

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

Nov 08, 2021

The c.484A>G (p.R162G) alteration is located in exon 3 (coding exon 2) of the TRIM43B gene. This alteration results from a A to G substitution at nucleotide position 484, causing the arginine (R) at amino acid position 162 to be replaced by a glycine (G). 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	0.090
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.49
DEOGEN2	Benign	0.015	T;T
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.20	T;.
MetaRNN	Benign	0.026	T;T
MutationAssessor	Benign	0.26	N;N
PrimateAI	Benign	0.46	T
GERP RS		-2.2
Varity_R		0.063
gMVP		0.064

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs769456796; hg19: chr2-96147366;