19-9830138-C-T

Variant names:

• chr19-9830138-C-T
• rs2287839
• ENST00000731112.1:n.376G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000731112.1(PIN1-DT):​n.376G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,047,856 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: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: PIN1-DT ENST00000731112.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 0 publications found

Genes affected

PIN1-DT (HGNC:55303): (PIN1 divergent transcript)

UBL5 (HGNC:13736): (ubiquitin like 5) This gene encodes a member of a group of proteins similar to ubiquitin. The encoded protein is not thought to degrade proteins like ubiquitin but to affect their function through being bound to target proteins by an isopeptide bond. The gene product has been studied as a link to predisposition to obesity based on its expression in Psammomys obesus, the fat sand rat, which is an animal model for obesity studies. Variation in this gene was found to be significantly associated with some metabolic traits (PMID: 15331561) but not associated with childhood obesity (PMID: 19189687). Pseudogenes of this gene are located on chromosomes 3, 5 and 17. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000731112.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBL5	NM_001048241.3	MANE Select	c.*130C>T		downstream_gene	N/A	NP_001041706.1
	UBL5	NM_024292.4		c.*130C>T		downstream_gene	N/A	NP_077268.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIN1-DT	ENST00000731112.1		n.376G>A		non_coding_transcript_exon	Exon 3 of 4
	UBL5	ENST00000586895.6	TSL:1 MANE Select	c.*130C>T		downstream_gene	N/A	ENSP00000468656.1
	UBL5	ENST00000358666.7	TSL:1	c.*130C>T		downstream_gene	N/A	ENSP00000351492.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000191 AC: 2 AN: 1047856 Hom.: 0 Cov.: 13 AF XY: 0.00000189 AC XY: 1 AN XY: 528666

African (AFR) AF: 0.00 AC: 0 AN: 24898

American (AMR) AF: 0.00 AC: 0 AN: 35902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19992

East Asian (EAS) AF: 0.00 AC: 0 AN: 36750

South Asian (SAS) AF: 0.00 AC: 0 AN: 68254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3222

European-Non Finnish (NFE) AF: 0.00000260 AC: 2 AN: 768728

Other (OTH) AF: 0.00 AC: 0 AN: 46016

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.91
PhyloP100		-0.062

Splicing

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

Other links and lift over

dbSNP: rs2287839; hg19: chr19-9940814;