rs1840123531

Variant names:

• chr20-3071650-C-CGCACCATGGCCG
• rs1840123531
• NM_000915.4:c.-3_9dupACCATGGCCGGC

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_000915.4(OXT):​c.-3_9dupACCATGGCCGGC​(p.Gly3_Pro4insThrMetAlaGly) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,450,324 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: OXT NM_000915.4 conservative_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.87

Genes affected

OXT (HGNC:8528): (oxytocin/neurophysin I prepropeptide) This gene encodes a precursor protein that is processed to produce oxytocin and neurophysin I. Oxytocin is a posterior pituitary hormone which is synthesized as an inactive precursor in the hypothalamus along with its carrier protein neurophysin I. Together with neurophysin, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis, where it is either stored or secreted into the bloodstream. The precursor seems to be activated while it is being transported along the axon to the posterior pituitary. This hormone contracts smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions. [provided by RefSeq, Dec 2013]

LOC101929098 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000915.4.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXT	NM_000915.4	c.-3_9dupACCATGGCCGGC	p.Gly3_Pro4insThrMetAlaGly	conservative_inframe_insertion	Exon 1 of 3	ENST00000217386.2	NP_000906.1
LOC101929098	XR_430278.4	n.103+535_103+546dupCGGCCATGGTGC		intron_variant	Intron 1 of 1
LOC101929098	XR_007067503.1	n.-39_-28dupCGGCCATGGTGC		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXT	ENST00000217386.2	c.-3_9dupACCATGGCCGGC	p.Gly3_Pro4insThrMetAlaGly	conservative_inframe_insertion	Exon 1 of 3	1	NM_000915.4	ENSP00000217386.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000483 AC: 7 AN: 1450324 Hom.: 0 Cov.: 31 AF XY: 0.00000693 AC XY: 5 AN XY: 721542

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder Uncertain:1

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1840123531; hg19: chr20-3052296;