20-3753867-T-G

Variant names:

• chr20-3753867-T-G
• rs2295340
• NM_001258429.2:c.*191A>C

Variant summary

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

The NM_001258429.2(ADISSP):​c.*191A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000223 in 447,764 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: ADISSP NM_001258429.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 10 publications found

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

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 (BayesDel_noAF=-0.3).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADISSP	NM_001258429.2	c.*191A>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000379772.4	NP_001245358.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADISSP	ENST00000379772.4	c.*191A>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_001258429.2	ENSP00000369097.4
ADISSP	ENST00000217195.12	c.*191A>C		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000217195.8
ADISSP	ENST00000399672.5	c.*191A>C		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000382580.1
ADISSP	ENST00000399683.7	c.*191A>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000382591.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000223 AC: 1 AN: 447764 Hom.: 0 Cov.: 3 AF XY: 0.00000423 AC XY: 1 AN XY: 236406

African (AFR) AF: 0.00 AC: 0 AN: 12168

American (AMR) AF: 0.00 AC: 0 AN: 19404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13648

East Asian (EAS) AF: 0.00 AC: 0 AN: 30130

South Asian (SAS) AF: 0.00 AC: 0 AN: 46212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3582

European-Non Finnish (NFE) AF: 0.00000375 AC: 1 AN: 266758

Other (OTH) AF: 0.00 AC: 0 AN: 26008

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.25

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

Other links and lift over

dbSNP: rs2295340; hg19: chr20-3734514;