chr3-8752859-G-C

Variant names:

• chr3-8752859-G-C
• rs1042778
• NM_000916.4:c.*118C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000916.4(OXTR):​c.*118C>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 0.0000226 in 974,770 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: 31)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: OXTR NM_000916.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• Publications: 134 publications found

Genes affected

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

CAV3 Gene-Disease associations (from GenCC):

• caveolinopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1C

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• long QT syndrome 9

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• rippling muscle disease 2

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• distal myopathy, Tateyama type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• inherited rippling muscle disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Brugada syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• long QT syndrome

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High AC in GnomAdExome4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000916.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXTR	NM_000916.4	MANE Select	c.*118C>G		3_prime_UTR	Exon 4 of 4	NP_000907.2
	OXTR	NM_001354653.2		c.*118C>G		3_prime_UTR	Exon 5 of 5	NP_001341582.1	B2R9L7
	OXTR	NM_001354654.2		c.*118C>G		3_prime_UTR	Exon 4 of 4	NP_001341583.1	P30559

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXTR	ENST00000316793.8	TSL:1 MANE Select	c.*118C>G		3_prime_UTR	Exon 4 of 4	ENSP00000324270.2	P30559
	OXTR	ENST00000894689.1		c.*118C>G		3_prime_UTR	Exon 4 of 4	ENSP00000564748.1
	OXTR	ENST00000894690.1		c.*118C>G		3_prime_UTR	Exon 4 of 4	ENSP00000564749.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000226 AC: 22 AN: 974770 Hom.: 0 Cov.: 13 AF XY: 0.0000228 AC XY: 11 AN XY: 483014

African (AFR) AF: 0.00 AC: 0 AN: 22342

American (AMR) AF: 0.00 AC: 0 AN: 20054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17020

East Asian (EAS) AF: 0.00 AC: 0 AN: 33426

South Asian (SAS) AF: 0.00 AC: 0 AN: 56470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3070

European-Non Finnish (NFE) AF: 0.0000294 AC: 22 AN: 748444

Other (OTH) AF: 0.00 AC: 0 AN: 43274

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 26143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.056
DANN	Benign	0.32
PhyloP100		-2.1

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

Other links and lift over

dbSNP: rs1042778; hg19: chr3-8794545;