2-95480399-C-A

Variant names:

• chr2-95480399-C-A
• rs563777718
• NM_001164464.2:c.644G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164464.2(TRIM43B):​c.644G>T​(p.Ser215Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S215N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIM43B NM_001164464.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1940068).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164464.2. 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
	TRIM43B	NM_001164464.2	MANE Select	c.644G>T	p.Ser215Ile	missense	Exon 4 of 7	NP_001157936.1	A6NCK2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM43B	ENST00000639673.3	TSL:1 MANE Select	c.644G>T	p.Ser215Ile	missense	Exon 4 of 7	ENSP00000492719.1	A6NCK2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457624 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724924

African (AFR) AF: 0.00 AC: 0 AN: 33122

American (AMR) AF: 0.00 AC: 0 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39334

South Asian (SAS) AF: 0.00 AC: 0 AN: 85468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109826

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_noAF	Benign	-0.91
CADD	Benign	11
DANN	Benign	0.35
DEOGEN2	Benign	0.098	T
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.19	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.032
PrimateAI	Uncertain	0.59	T
GERP RS		0.40
Varity_R		0.095
gMVP		0.17

Splicing

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

Other links and lift over

dbSNP: rs563777718; hg19: chr2-96146147;