chr20-3753867-T-C

Position:

• chr20-3753867-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001258429.2(ADISSP):​c.*191A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 597,928 control chromosomes in the GnomAD database, including 33,247 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 0.30 (7285 hom., cov: 33)
  • Exomes 𝑓: 0.33 (25962 hom.)
• Consequence: ADISSP NM_001258429.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247

Genes affected

ADISSP (HGNC:15873): (adipose secreted signaling protein) Enables protein phosphatase 1 binding activity. Involved in positive regulation of NIK/NF-kappaB signaling and positive regulation of transforming growth factor beta receptor signaling pathway. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADISSP	NM_001258429.2	c.*191A>G		3_prime_UTR_variant	6/6	ENST00000379772.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADISSP	ENST00000379772.4	c.*191A>G		3_prime_UTR_variant	6/6	1	NM_001258429.2	P1
ADISSP	ENST00000217195.12	c.*191A>G		3_prime_UTR_variant	6/6	2
ADISSP	ENST00000399672.5	c.*191A>G		3_prime_UTR_variant	6/6	2		P1
ADISSP	ENST00000399683.7	c.*191A>G		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45001 AN: 150594 Hom.: 7279 Cov.: 33

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.335 AC: 149605 AN: 447214 Hom.: 25962 Cov.: 3 AF XY: 0.333 AC XY: 78693 AN XY: 236154

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.328

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.327

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.299 AC: 45027 AN: 150714 Hom.: 7285 Cov.: 33 AF XY: 0.302 AC XY: 22228 AN XY: 73694

Gnomad4 AFR AF: 0.179

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.269

Alfa AF: 0.328 Hom.: 2609

Bravo AF: 0.283

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2295340; hg19: chr20-3734514;