chr3-8753081-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000916.4(OXTR):c.1066C>T(p.Arg356Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000719 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000072 ( 0 hom. )
Consequence
OXTR
NM_000916.4 missense
NM_000916.4 missense
Scores
4
15
Clinical Significance
Conservation
PhyloP100: 3.66
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22093251).
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OXTR | NM_000916.4 | c.1066C>T | p.Arg356Cys | missense_variant | 4/4 | ENST00000316793.8 | NP_000907.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OXTR | ENST00000316793.8 | c.1066C>T | p.Arg356Cys | missense_variant | 4/4 | 1 | NM_000916.4 | ENSP00000324270.2 | ||
CAV3 | ENST00000472766.1 | n.155+19091G>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251360Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135858
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GnomAD4 exome AF: 0.0000718 AC: 105AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.0000688 AC XY: 50AN XY: 727244
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74336
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 23, 2021 | The c.1066C>T (p.R356C) alteration is located in exon 4 (coding exon 2) of the OXTR gene. This alteration results from a C to T substitution at nucleotide position 1066, causing the arginine (R) at amino acid position 356 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of solvent accessibility (P = 0.0036);
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at