rs10518384

Positions:

• chr4-121178365-G-C

Variant summary

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

The NM_001244764.2(TNIP3):​c.210+4311C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0514 in 152,292 control chromosomes in the GnomAD database, including 321 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 0.051 (321 hom., cov: 32)
• Consequence: TNIP3 NM_001244764.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672

Genes affected

TNIP3 (HGNC:19315): (TNFAIP3 interacting protein 3) Enables polyubiquitin modification-dependent protein binding activity. Involved in cellular response to lipopolysaccharide; negative regulation of I-kappaB kinase/NF-kappaB signaling; and toll-like receptor signaling pathway. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNIP3	NM_001244764.2	c.210+4311C>G		intron_variant			NP_001231693.1
TNIP3	NM_001128843.2	c.189+4311C>G		intron_variant			NP_001122315.2
TNIP3	XM_011532256.3	c.300+4059C>G		intron_variant			XP_011530558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNIP3	ENST00000509841.1	c.210+4311C>G		intron_variant		2		ENSP00000426613.1
TNIP3	ENST00000507879.5	c.189+4311C>G		intron_variant		2		ENSP00000427106.1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7801 AN: 152174 Hom.: 315 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0158

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0248

Gnomad OTH AF: 0.0388

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0514 AC: 7829 AN: 152292 Hom.: 321 Cov.: 32 AF XY: 0.0530 AC XY: 3948 AN XY: 74468

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.0248

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0419 Hom.: 26

Bravo AF: 0.0530

Asia WGS AF: 0.0250 AC: 90 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.23
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518384; hg19: chr4-122099520;