ENST00000602596.1:n.137-375C>T

Variant names:

• chr16-67483735-C-T
• rs34018897
• ENST00000602596.1:n.137-375C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000602596.1(ATP6V0D1-DT):​n.137-375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 177,134 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: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: ATP6V0D1-DT ENST00000602596.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800

Genes affected

ATP6V0D1-DT (HGNC:55268): (ATP6V0D1 divergent transcript)

AGRP (HGNC:330): (agouti related neuropeptide) This gene encodes an antagonist of the melanocortin-3 and melanocortin-4 receptor. It appears to regulate hypothalamic control of feeding behavior via melanocortin receptor and/or intracellular calcium regulation, and thus plays a role in weight homeostasis. Mutations in this gene have been associated with late on-set obesity. [provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
AGRP	NM_001138.2	c.-222G>A		upstream_gene_variant		ENST00000290953.3	NP_001129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGRP	ENST00000290953.3	c.-222G>A		upstream_gene_variant		1	NM_001138.2	ENSP00000290953.3

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152160 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00193 AC: 48 AN: 24856 Hom.: 0 Cov.: 0 AF XY: 0.00193 AC XY: 24 AN XY: 12422

Gnomad4 AFR exome AF: 0.00198

Gnomad4 AMR exome AF: 0.00360

Gnomad4 ASJ exome AF: 0.00181

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00313

Gnomad4 FIN exome AF: 0.000782

Gnomad4 NFE exome AF: 0.00219

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152278 Hom.: 0 Cov.: 33 AF XY: 0.00118 AC XY: 88 AN XY: 74462

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000785

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00161 Hom.: 0

Bravo AF: 0.00116

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	10
DANN	Benign	0.84

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: rs34018897; hg19: chr16-67517638;